How Vitamin D Impacts Brain Health, Cognitive Performance and Neuroprotection
- Dr Oliver Finlay
- Jul 1
- 23 min read
Dr Oliver Finlay
KEY POINTS
• Vitamin D receptors in the brain influence memory, learning, and neuroprotection.
• Deficiency in vitamin D is linked to cognitive decline and increased dementia risk.
• Vitamin D regulates inflammation, oxidative stress, and neurotrophic factors like BDNF.
• Supplementation may improve cognition, especially in deficient or at-risk individuals.
• Research supports a link between vitamin D supplementation and cognitive performance and brain health but more targeted clinical trials are needed.
Introduction
Vitamin D is a fat soluble, essential nutrient that is best known for its role in maintaining healthy bones. However, in recent years, researchers have found that it also plays a significant role in brain health and cognitive function. Low levels of vitamin D have been linked to poorer memory, slower thinking, and even an increased risk of dementia. On the other hand, there is growing interest in whether vitamin D supplementation could improve brain function or even help prevent neurodegenerative diseases like Alzheimer’s.
This essay explores how vitamin D affects the brain, what happens when levels are too low, and whether taking supplements can really make a difference.
The Brain’s Relationship with Vitamin D
Vitamin D receptors are found throughout the brain, especially in areas involved in memory and learning, such as the hippocampus and prefrontal cortex (Eyles et al., 2005). These receptors allow vitamin D to act like a hormone, influencing the expression of genes involved in brain development and function.
Research also shows that vitamin D plays a role in reducing inflammation and oxidative stress in the brain—both of which are linked to cognitive decline and diseases like Alzheimer’s (Garvin & Kemper, 2013; Sailike et al., 2024).
Furthermore, vitamin D helps regulate the production of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which supports neuron growth and survival (Dewi et al., 2025; Hoseini et al., 2023). This supports the idea that vitamin D is not only protective but potentially restorative in the nervous system.
Consequences of Low Vitamin D on Cognitive Function
Many studies have shown that low vitamin D levels are associated with cognitive problems. For example, a large-scale study by Littlejohns et al. (2014) found that people with severe vitamin D deficiency were over twice as likely to develop dementia or Alzheimer’s disease. Similarly, Wilkins et al. (2006) found a clear association between low vitamin D levels and worse cognitive performance, especially in older adults.
Systematic reviews by Annweiler et al. (2009, 2013) have consistently confirmed that low vitamin D is correlated with impaired cognitive performance, especially in tasks involving executive function, processing speed, and memory. These reviews, while compelling, also acknowledge limitations such as variability in how cognition is measured and potential confounding factors like physical health and sun exposure.
Animal studies also support this link. For instance, Lin et al. (2020) found that vitamin D deficiency in mice worsened cognitive impairment in an Alzheimer's disease model, possibly through mechanisms involving collapsin response mediator protein-2 (CRMP2), a protein that affects neuron structure.
How Vitamin D Impacts the Brain Neurophysiologically
At a biological level, vitamin D contributes to brain health in several key ways. It helps regulate calcium in neurons, supports the release of neurotransmitters, and protects against inflammation (Máčová et al., 2023). It also influences neurogenesis (the creation of new neurons) and helps maintain the blood–brain barrier.
Vitamin D’s interaction with the immune system is especially important in neurodegenerative diseases. Chronic brain inflammation is a key contributor to diseases like Alzheimer’s and Parkinson’s. Vitamin D helps suppress this inflammation by downregulating pro-inflammatory cytokines (Cui & Eyles, 2022), reducing damage to brain cells over time.
In children, vitamin D is linked to the production of BDNF, NGF (nerve growth factor), and GDNF (glial cell-derived neurotrophic factor), all of which are essential for healthy brain development (Dewi et al., 2025).
Supplementation: A Cognitive Performance Enhancer or Therapeutic Tool?
Given this background, can taking vitamin D supplements help improve cognitive function or prevent decline? The evidence is mixed, but promising.
Jahrami et al. (2019) conducted a meta-analysis of several clinical trials and found that vitamin D supplementation slightly improved cognitive performance in older adults who were deficient. However, the benefits were generally modest and more evident in people with very low starting levels.
A more recent study by Ghahremani et al. (2023) suggested that vitamin D supplementation reduced the risk of dementia, especially in women and those with a certain genetic risk factor (APOE ε4). This highlights how vitamin D may be more effective in certain populations or in combination with other treatments.
Maddock et al. (2017), using Mendelian randomisation (a method that uses genetics to test for causality), found a potential causal relationship between low vitamin D and reduced cognitive function. This strengthens the argument that the association is not merely due to other lifestyle factors.
Nevertheless, not all studies agree. Aspell et al. (2018) caution that while low vitamin D is clearly associated with poorer cognitive performance, evidence that supplementation actually improves brain function is less robust. Factors such as dosage, duration of treatment, and individual variability complicate the picture.
Strengths and Limitations in the Research
The strongest studies use large sample sizes, control for confounding variables, and include longitudinal data (e.g., Littlejohns et al., 2014). Studies like Maddock et al. (2017) use genetic approaches to reduce bias, which adds weight to their conclusions.
However, many studies are observational and can’t prove cause and effect. Cognitive performance can also be influenced by many other factors—such as physical activity, diet, education, and social engagement—making it hard to isolate the effects of vitamin D alone.
Clinical trials are limited by small sample sizes, short durations, and differences in how vitamin D levels are measured. There is also ongoing debate about what counts as a “deficient” level of vitamin D.
Conclusion
Vitamin D plays a vital role in brain health, influencing everything from inflammation to neuron growth to neurotransmission. Low levels are consistently linked to poorer cognitive performance and a higher risk of dementia, while supplementation may offer protective or even restorative effects—particularly in those who are deficient or genetically at risk.
While further research is needed to fully understand who benefits most and under what conditions, it is clear that maintaining healthy vitamin D levels is important not just for bones, but for brains as well.
References & Scientific Power Evaluation
Annweiler, C., Allali, G., Allain, P., Bridenbaugh, S., Schott, A.-M., Kressig, R.W. and Beauchet, O., 2009. Vitamin D and cognitive performance in adults: A systematic review. European Journal of Neurology, 16(10), pp.1083-1089.
OVERVIEW: This article presents a systematic review of existing studies on the relationship between vitamin D levels and cognitive performance in adults. The authors searched for and analysed multiple observational studies to determine whether low vitamin D levels are linked to poorer cognitive function. The review focuses on older adults and aims to clarify if vitamin D plays a role in maintaining brain health.
STRENGTHS: This article systematically gathers evidence from multiple studies, which helps provide a broader understanding of the topic. It includes research from different countries and uses clear criteria for selecting studies, enhancing the review's reliability. The article is also well-structured and written in a way that highlights patterns across the research, particularly noting consistent associations between low vitamin D levels and cognitive decline in older adults.
LIMITATIONS: Most of the studies included in the review are observational, meaning they can only show a correlation, not causation. This makes it difficult to know whether low vitamin D causes cognitive problems or if other factors are involved (e.g., poor health or less time outdoors). The review also includes studies that vary widely in design and cognitive assessments, which reduces comparability. Additionally, it doesn’t explore intervention studies where vitamin D supplementation was tested, which would have added practical insight.
CONCLUSION: The review concludes that there is a consistent link between low vitamin D levels and reduced cognitive performance in adults, especially the elderly. However, due to the limitations of the included studies, further research—especially clinical trials—is needed to confirm causality.
SCIENTIFIC POWER: MODERATE - It is based on a solid collection of studies and provides important insights, but its conclusions are limited by the observational nature and variability of the included research.
Annweiler, C., et al., 2013. Vitamin D and cognition in older adults: Updated international review and recommendations. Journal of the American Geriatrics Society, 61(2), pp.179–183.
OVERVIEW: The article provides an updated review of existing studies on how vitamin D might affect thinking, memory, and overall brain health in older adults. It summarises findings from observational studies, experimental research, and clinical trials. Based on the available evidence, the authors also offer expert recommendations on vitamin D intake and further research needed in this area.
STRENGTHS: One of the key strengths of this paper is its international perspective. The review includes studies from various countries and research settings, making its findings more globally relevant. It also combines different types of studies—like lab experiments and population-based research—which helps give a more complete picture. The authors go a step further by offering practical advice for health professionals and policymakers, such as suggested vitamin D levels for older adults.
LIMITATIONS: Most of the studies it discusses are observational, meaning they can only show a link between low vitamin D and poor cognitive function—they can’t prove one causes the other. There is also little discussion about the quality of the included studies, such as sample sizes or how well they controlled for confounding factors like age, health status, or sun exposure. Furthermore, the article does not include a meta-analysis, which would have provided a stronger statistical summary of the data.
CONCLUSION: This review suggests that maintaining adequate vitamin D levels may support better cognitive function in older adults. However, more controlled studies are needed to confirm if vitamin D directly improves brain health.
SCIENTIFIC POWER: MODERATE - It offers a well-informed summary and helpful recommendations, but its reliance on observational studies and lack of detailed methodological critique limits the strength of its conclusions.
Aspell, N., Lawlor, B. and O’Sullivan, M., 2018. Is there a role for vitamin D in supporting cognitive function as we age? Proceedings of the Nutrition Society, 77(2), pp.124-134.
OVERVIEW: This article explores whether vitamin D plays a role in maintaining brain health and cognitive function as people grow older. The authors review existing research, including observational studies and some clinical trials, to evaluate if vitamin D could help prevent or slow cognitive decline. They also discuss how vitamin D might affect the brain biologically, such as by reducing inflammation and supporting nerve health.
STRENGTHS: The article takes a well-rounded approach. It not only looks at human studies but also explains how vitamin D works in the brain on a biological level. This helps the reader understand both the potential benefits and the reasons behind them. The article is also current and includes a broad range of sources, making it a good summary of where the research stands on this topic.
LIMITATIONS: Most of the existing studies are observational, meaning they can only show a connection between low vitamin D and poor cognitive function—not prove that one causes the other. The clinical trials that do exist often show mixed results, with some finding benefits and others finding none. The authors also acknowledge that factors like age, health conditions, and vitamin D dosage vary widely across studies, making it difficult to draw clear conclusions.
CONCLUSION: The article concludes that while vitamin D likely plays a role in brain health, there is not enough strong evidence yet to say for sure that supplements will improve cognitive function as we age.
SCIENTIFIC POWER: MODERATE - It is thoughtful and evidence-based but limited by the quality and consistency of the studies it discusses.
Cui, X. and Eyles, D.W., 2022. Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders. Nutrients, 14(20), p.4353.
OVERVIEW: The article explores how vitamin D affects the brain and whether it could help prevent or treat certain brain disorders. This review focuses on the biological mechanisms of vitamin D in the central nervous system (CNS), including its role in brain development, inflammation control, and protection against damage. The authors summarise research from lab studies, animal models, and some human evidence, with a focus on conditions like schizophrenia, multiple sclerosis, and Alzheimer’s disease.
STRENGTHS: A major strength of this article is its strong focus on the biological science behind vitamin D’s effects on the brain. It explains how vitamin D may protect neurons (nerve cells), reduce inflammation, and influence brain development and function. This helps connect what happens at the molecular level with possible mental health outcomes. The paper also reviews a wide range of disorders, giving a broad picture of vitamin D’s potential importance.
LIMITATIONS: The main limitation of this article is that much of the evidence comes from animal studies and lab-based experiments, which may not directly apply to humans. While some human studies are mentioned, the article doesn’t focus much on clinical trials or real-world data. This makes it difficult to know how useful vitamin D truly is in preventing or treating brain disorders in people. Also, the article does not compare the strength of different types of studies, which limits critical evaluation.
CONCLUSION: This review suggests vitamin D may influence brain health and help prevent or manage some brain disorders. However, more high-quality human studies are needed to prove these benefits.
SCIENTIFIC POWER: MODERATE to STRONG - The article is thorough, biologically detailed, and well-referenced, but its reliance on preclinical (non-human) evidence limits the strength of its real-world conclusions.
Dewi, M.M., Imron, A., Risan, N.A., Mediana, G., Judistiani, R.T.D. and Setiabudiawan, B., 2025. The Association of Vitamin D, Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Cell-Derived Neurotrophic Factor (GDNF) with Development in Children. Children, 12(1), p.60.
OVERVIEW: The article investigates how vitamin D levels are related to certain brain-related proteins—NGF, BDNF, and GDNF—in children. These proteins are important for brain development and function. The study looks at blood samples from children to see if there is a connection between vitamin D and these growth factors, which play key roles in learning, memory, and overall brain health.
STRENGTHS: The study focuses on children, a group that is often underrepresented in vitamin D research. By looking at biological markers (like NGF and BDNF), the researchers provide insight into how vitamin D might influence early brain development. The use of blood tests also allows for objective measurement of both vitamin D and the neurotrophic factors, adding reliability to the data. This gives the study a valuable biological foundation.
LIMITATIONS: The study is observational, which means it can only show a relationship, not prove that vitamin D causes changes in brain development. Also, the sample size is relatively small and limited to a specific population, which makes it harder to apply the findings to all children. The article does not explore long-term cognitive outcomes, so it is unclear how these biological associations might affect learning or behaviour over time.
CONCLUSION: This study suggests a possible link between vitamin D and important brain growth factors in children, indicating vitamin D may play a role in healthy brain development. However, more research is needed to confirm this.
SCIENTIFIC POWER: MODERATE - It is well-designed and biologically grounded, but its observational nature and limited scope reduce the strength of its conclusions.
Eyles, D.W., Smith, S., Kinobe, R., Hewison, M. and McGrath, J.J., 2005. Development of the vitamin D system in the human brain. Birth Defects Research Part A: Clinical and Molecular Teratology, 73(10), pp.756-760.
OVERVIEW: The study investigates whether the human brain has its own functioning vitamin D system during early development. The researchers examined human brain tissue samples at different stages of foetal growth to detect the presence of vitamin D receptors (VDR) and enzymes needed to activate vitamin D. Their goal was to determine if vitamin D might play a direct role in how the brain develops before birth.
STRENGTHS: A key strength of this study is its unique focus on foetal brain development, a stage that is often hard to study directly. By examining real human brain tissue, the researchers provide strong biological evidence that the brain can both respond to and process vitamin D. This supports the idea that vitamin D may influence brain development from a very early age. The use of molecular techniques to detect specific proteins also adds precision and scientific credibility to the findings.
LIMITATIONS: The study is limited by its small sample size and descriptive nature. It does not link the presence of vitamin D systems in the brain to any specific developmental outcomes, such as cognitive function or mental health. It also doesn’t test how changes in vitamin D levels might affect brain development—so while it suggests potential importance, it stops short of showing real-world effects.
CONCLUSION: This research provides early evidence that vitamin D plays a role in brain development by showing that the brain can use vitamin D even before birth. It lays the groundwork for future studies on the importance of prenatal vitamin D.
SCIENTIFIC POWER: MODERATE to STRONG - The study offers rare and valuable human data and uses reliable methods. However, it does not explore outcomes or establish cause-and-effect relationships.
Fang-Yu Lin, F.-Y., et al., 2020. Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2. Neuropharmacology, 164, p.107910.
OVERVIEW: The study examines how a deficiency in vitamin D3 affects cognitive performance in mice genetically modified to mimic Alzheimer’s disease. The researchers focused on a brain protein called collapsin response mediator protein-2 (CRMP2), which helps with brain cell communication and structure. They found that low vitamin D3 levels were linked to worse memory and learning in the mice, possibly due to abnormal activity of CRMP2.
STRENGTHS: The study uses a well-established animal model for Alzheimer’s disease, which allows researchers to closely monitor brain changes and behaviour in a controlled setting. The experiment included both behavioural testing (to assess learning and memory) and molecular analysis (to study protein changes in the brain), giving a more complete picture of how vitamin D3 might affect cognition. Additionally, the research explores a novel pathway—CRMP2—which could be a new target for understanding Alzheimer’s disease.
LIMITATIONS: The study is limited by its use of animals. While mice are often used in brain research, their brains are not identical to humans’, so the results may not fully apply to people. Also, the researchers did not test whether giving vitamin D3 supplements could reverse the cognitive problems, so the study only shows the effect of deficiency, not the potential benefits of treatment.
CONCLUSION: This study supports the idea that vitamin D3 deficiency can worsen cognitive decline, especially in Alzheimer’s disease, and suggests CRMP2 may be involved. However, more research in humans is needed.
SCIENTIFIC POWER: MODERATE - The study uses a strong experimental design and adds new ideas but is based on animal models, limiting how directly the results apply to humans.
Garvin, D.S. and Kemper, J.K., 2013. The influence of vitamin D receptor signaling on control of oxidative stress and inflammation. Frontiers in Physiology, 4, p.275.
OVERVIEW: The article explores how vitamin D affects the body’s ability to manage oxidative stress and inflammation—two processes that are linked to brain damage and many chronic diseases. The authors focus on the vitamin D receptor (VDR), a special protein in cells that helps the body respond to vitamin D. They explain how VDR signaling can regulate certain genes that reduce harmful free radicals and control inflammatory responses, which may help protect brain cells and other tissues.
STRENGTHS: This article provides a strong biological explanation for how vitamin D might protect the brain and body. The authors highlight how VDR activation reduces oxidative stress and inflammation—both of which are known to damage neurons and contribute to diseases like Alzheimer’s and Parkinson’s. It also draws on a range of studies, including molecular and genetic research, to support its claims. These details help explain why vitamin D may have protective effects, not just whether it does.
LIMITATIONS: While the article is strong on theory and cellular biology, it doesn’t include human or clinical studies. This means it doesn’t show how these processes impact real people in terms of cognitive performance or disease prevention. The focus is very narrow, mostly dealing with molecular pathways rather than practical or clinical outcomes. It also assumes a fair amount of scientific background, which may be challenging for less experienced readers.
CONCLUSION: The article offers helpful insights into the molecular role of vitamin D and its receptor in reducing cell damage and inflammation, which may help explain its benefits for brain health.
SCIENTIFIC POWER: MODERATE to STRONG - The article provides detailed, well-supported biological mechanisms, but lacks human evidence to confirm these effects in everyday health contexts.
Ghahremani, M., et al., 2023. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer’s & Dementia (Amsterdam), 15(1), pp.e12404.
OVERVIEW: The article investigates whether taking vitamin D supplements can reduce the risk of developing dementia. The study followed over 12,000 older adults who did not have dementia at the start and tracked whether they later developed it. The researchers also examined how different factors—such as sex, APOE gene status (a genetic risk factor for Alzheimer’s), and baseline cognitive function—affected the relationship between vitamin D use and dementia risk.
STRENGTHS: This study is notable for its large sample size and long-term follow-up, which gives the findings more reliability. It used real-world data from the National Alzheimer’s Coordinating Center (NACC), making the results more applicable to general populations. The study also explores how individual differences, like genetics and early cognitive status, influence the effect of vitamin D supplementation—something many studies overlook. Importantly, the authors found that vitamin D use was associated with a significantly lower risk of dementia, especially in women and those with normal cognition at baseline.
LIMITATIONS: The study is observational, meaning it shows association, not causation. People who take vitamin D might also be healthier in other ways, which could affect the results. Supplement type and dosage varied, which could influence how strong the effects were. There’s also no clear information on whether the participants had vitamin D deficiencies to begin with, which is important when interpreting results.
CONCLUSION: This study suggests that vitamin D supplementation may reduce the risk of dementia, particularly in certain groups. However, more controlled trials are needed to confirm cause and effect.
SCIENTIFIC POWER: MODERATE to STRONG - The large sample size, real-world data, and thoughtful subgroup analysis are strengths, although limitations of observational design prevent a full "STRONG" rating.
Hoseini, R., Hoseini, Z. and Bahmani, E., 2023. Combined Exercise and Vitamin D on Brain-Derived Neurotrophic Factor. Biochemistry. IntechOpen. Available at: http://dx.doi.org/10.5772/intechopen.112021.
OVERVIEW: This article reviews how combining exercise with vitamin D supplementation may influence brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of brain cells. BDNF is closely linked to learning, memory, and overall cognitive function. The authors summarize various studies showing that both exercise and vitamin D can raise BDNF levels and suggest that using them together might have a stronger effect than using either alone.
STRENGTHS: The main strength of this article is its focus on the combined impact of two well-known brain boosters: physical activity and vitamin D. It brings together findings from different types of studies, including clinical trials and animal research, giving a broader view of how these interventions might work together. The review format is also accessible, providing a clear overview of mechanisms without getting too technical, which makes it useful for students and early researchers.
LIMITATIONS: One limitation is that the article is more of a narrative review than a systematic one. This means it doesn’t clearly explain how studies were selected or evaluated, which may introduce bias. It also lacks new experimental data and sometimes draws conclusions without strong evidence from large human trials. The article could have gone further in addressing potential differences based on age, sex, or baseline health status.
CONCLUSION: This review supports the idea that combining exercise and vitamin D may enhance brain health through BDNF, but more research - especially in humans - is needed to confirm this effect.
SCIENTIFIC POWER: MODERATE - The article presents a reasonable theory supported by existing studies but lacks systematic methods and original data, limiting its strength.
Jahrami, H., et al., 2019. The effect of vitamin D supplementation on cognitive function in elderly individuals with low vitamin D levels: A systematic review and meta-analysis. Drug and Therapeutics Perspectives, 6(3), pp.103-109.
OVERVIEW: The systematic review and meta-analysis explore whether vitamin D supplementation improves cognitive function in older adults with low vitamin D levels. The authors gathered data from multiple studies to determine if taking vitamin D could enhance memory, attention, or overall thinking ability in elderly individuals who were vitamin D deficient.
STRENGTHS: A major strength of this article is its use of a systematic review and meta-analysis approach, which combines data from many studies to provide stronger and more reliable conclusions. The researchers followed a clear process to select studies, helping reduce bias. By focusing on a specific group—older adults with low vitamin D levels—the findings are more relevant and targeted. This is important since this population is at high risk for both cognitive decline and vitamin D deficiency.
LIMITATIONS: The included studies vary in their quality, sample sizes, and the dosage and duration of vitamin D supplements used, which affects the strength of the conclusions. The improvements in cognitive performance reported were often small and inconsistent across studies. Additionally, some of the studies did not control for other factors (like physical activity or overall health) that might have influenced cognitive outcomes.
CONCLUSION: The article concludes that vitamin D supplementation may offer mild cognitive benefits for older adults with low vitamin D levels, but the evidence is not strong enough to recommend it as a treatment on its own.
SCIENTIFIC POWER: MODERATE to STRONG - The systematic review and meta-analysis design adds credibility, though variation in study quality and inconsistent results prevent a full “STRONG” rating.
Landel, V., Annweiler, C., Millet, P., Morello, M., Féron, F. and Wion, D., 2016. Vitamin D, Cognition and Alzheimer’s Disease: The Therapeutic Benefit is in the D-Tails. Journal of Alzheimer’s Disease, 53(2), pp.419–444.
OVERVIEW: The article reviews the role of vitamin D in brain health, with a specific focus on its connection to Alzheimer’s disease. The authors explore how vitamin D affects cognitive function and the biological mechanisms behind its potential protective effects, including its impact on inflammation, brain cell communication, and the build-up of harmful proteins in the brain.
STRENGTHS: This article stands out for its comprehensive approach, covering both clinical and laboratory research. It does a good job linking the biological effects of vitamin D—like reducing inflammation and improving brain plasticity—to real-world issues like memory loss and dementia. The authors also discuss how vitamin D interacts with other factors, such as genetics and aging, giving the article a balanced and informed perspective.
LIMITATIONS: One limitation is that, while the review covers a wide range of studies, many of the findings are from animal or cell-based research rather than large-scale clinical trials in humans. This means that the results are suggestive but not conclusive. Also, although the article discusses potential therapeutic uses of vitamin D, it doesn’t provide strong evidence from intervention studies to support treatment recommendations.
CONCLUSION: The article supports the idea that vitamin D may help protect against cognitive decline and Alzheimer’s disease, especially through its biological actions in the brain. However, it highlights the need for more human-based research before drawing firm conclusions about treatment.
SCIENTIFIC POWER: MODERATE to STRONG - The article has a strong theoretical foundation and wide review scope. However, the limited amount of direct human trial evidence keeps it from reaching a full “STRONG” rating.
Littlejohns, T.J., et al., 2014. Vitamin D and the risk of dementia and Alzheimer disease. Neurology, 83(10), pp.920–928.
OVERVIEW: The authors conducted a large prospective cohort study to examine whether low levels of vitamin D are linked to a higher risk of developing dementia and Alzheimer’s disease in older adults. The study followed over 1,600 participants for around six years, all of whom were free of dementia at the beginning. Researchers measured participants’ vitamin D levels and then tracked who developed dementia or Alzheimer’s over time.
STRENGTHS: One of the biggest strengths of this study is its large sample size and prospective design, which means participants were followed over time rather than just assessed once. This allows for stronger evidence of a possible link between low vitamin D and later development of dementia. The researchers controlled for many factors (such as age, education, and lifestyle) that could affect brain health, which makes the findings more reliable. They also found a clear “dose-response” relationship—those with the lowest vitamin D levels had the highest risk.
LIMITATIONS: While the study suggests a strong association, it still cannot prove that low vitamin D causes dementia. There could be other unknown factors at play, or it might be that early-stage dementia leads to lower vitamin D (e.g., through poor diet or less sunlight exposure). Also, vitamin D was only measured once at the beginning, which may not reflect long-term levels.
CONCLUSION: The study provides strong evidence of a link between low vitamin D levels and a higher risk of dementia and Alzheimer’s, but more experimental research is needed to confirm causation.
SCIENTIFIC POWER: STRONG - This study has a large sample, long follow-up, rigorous control of variables, and statistically significant results, even though it is observational.
Maddock, J., et al., 2017. Vitamin D and cognitive function: A Mendelian randomisation study. Scientific Reports, 7, p.13230.
OVERVIEW: The study uses a method called Mendelian randomisation to investigate whether vitamin D levels have a direct effect on cognitive function. This approach uses genetic variations linked to vitamin D levels to assess if people with genetically lower vitamin D also show worse cognitive performance. By doing this, the authors aimed to reduce the effects of confounding factors (like diet or lifestyle) that can influence results in observational studies.
STRENGTHS: One of the biggest strengths of this study is its use of Mendelian randomisation. This method is valuable because it mimics the structure of a randomised controlled trial by using genetics to predict vitamin D levels, which are determined at birth and not influenced by lifestyle. This makes it easier to test whether vitamin D truly causes changes in cognition. The study also included a large dataset, increasing the reliability of its findings.
LIMITATIONS: A key limitation is that the study found no strong evidence that genetically lower vitamin D levels affect overall cognitive ability. However, the genetic variations used only explained a small amount of the difference in vitamin D levels between people. This weak genetic instrument may reduce the study’s ability to detect an effect, even if one exists. Also, cognitive function was measured at a single point in time, rather than changes over the lifespan.
CONCLUSION: The study suggests that vitamin D might not directly influence cognitive function, but more research is needed, especially with stronger genetic markers and long-term cognitive measurements.
SCIENTIFIC POWER: MODERATE to STRONG - This study has an advanced and reliable methodology, despite limitations in genetic power and the interpretation of null results.
Máčová, L., Kancheva, R. and Bičíková, M., 2023. Molecular Regulation of the CNS by Vitamin D. Physiological Research, 72(Suppl. 4), pp.S339–S356.
OVERVIEW: The study reviews the molecular mechanisms by which vitamin D influences the central nervous system (CNS). The authors examine how vitamin D interacts with brain cells at the molecular level, focusing on its role in regulating gene expression, inflammation, neurotransmitter production, and neuroprotection. The article also discusses vitamin D’s potential in the context of neurodevelopmental and neurodegenerative disorders.
STRENGTHS: A major strength of this review is its deep dive into the biological and molecular processes that explain how vitamin D works in the brain. It summarises a wide range of recent studies, both in humans and animals, and provides detailed explanations about how vitamin D may protect brain cells and influence mental health. The paper also highlights the role of vitamin D receptors in various brain regions, which adds to its scientific depth.
LIMITATIONS: Much of the evidence comes from laboratory or animal studies, rather than large-scale clinical trials in humans. This limits the ability to confidently apply the findings to real-world medical practice. Additionally, the article is dense with technical language, which might make it difficult for less experienced readers to understand. Finally, it does not clearly identify gaps in current knowledge or make specific recommendations for future research.
CONCLUSION: This article provides strong theoretical and biological support for the importance of vitamin D in brain function. However, it also makes clear that more human-based research is needed to turn these ideas into practical treatments.
SCIENTIFIC POWER: MODERATE to STRONG - The molecular explanations are detailed and well-supported, but the lack of human clinical trial data prevents a full “STRONG” rating.
Sailike, B., Onzhanova, Z., Akbay, B., Tokay, T. and Molnár, F., 2024. Vitamin D in Central Nervous System: Implications for Neurological Disorders. International Journal of Molecular Sciences, 25(14), p.7809.
OVERVIEW: The article presents a comprehensive review of the role vitamin D plays in the central nervous system (CNS), especially regarding its involvement in neurological disorders like multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and depression. The article explores both the molecular mechanisms by which vitamin D functions in the brain and its potential clinical applications in preventing or treating these disorders.
Strength: The key strength of this paper is its broad and up-to-date coverage of neurological conditions and how they may be influenced by vitamin D. It explains complex processes—such as how vitamin D regulates inflammation, oxidative stress, and gene expression in brain cells—in a well-organised and accessible way. The authors reference a large number of recent studies, drawing on both animal and human research. The inclusion of potential therapeutic implications also adds practical value to the review.
LIMITATIONS: Despite its strengths, much of the data comes from observational or animal studies, which limits the ability to prove cause-and-effect relationships in humans. Furthermore, although the article summarises many studies, it does not always critically evaluate their quality or limitations. There is also limited discussion of randomised controlled trials, which are needed to confirm the therapeutic effects of vitamin D.
CONCLUSION: The article provides a strong foundation for understanding how vitamin D may influence brain health and neurological diseases. However, more human clinical studies are needed to translate these insights into medical treatments.
SCIENTIFIC POWER: MODERATE to STRONG - The review is well-researched and detailed, but it relies heavily on preclinical and observational evidence without enough support from interventional studies.
Wilkins, C.H., Sheline, Y.I., Roe, C.M., Birge, S.J. and Morris, J.C., 2006. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. American Journal of Geriatric Psychiatry, 14(12), pp.1032–1040.
OVERVIEW: The article explores the relationship between vitamin D levels, mood, and cognitive function in older adults. The study aimed to find out whether people with lower levels of vitamin D also performed worse on cognitive tests and reported lower mood. The researchers collected data from a sample of community-dwelling older adults and used statistical analysis to determine associations.
STRENGTHS: One strength of this study is its focus on a real-world population of older adults, which makes the findings more relevant for public health. The researchers used well-established cognitive tests and mood assessments, adding to the reliability of the results. Additionally, the study helped bring attention to vitamin D as a possible factor in cognitive and emotional health, especially in aging populations.
LIMITATIONS: The study is observational, meaning it can show a link but not prove that low vitamin D causes poor mood or cognitive decline. Other factors like poor diet, chronic illness, or reduced physical activity might also explain the results. Also, the sample size was relatively small, which can reduce the strength of the conclusions and limit how well the findings apply to the wider population.
CONCLUSION: This study suggests that low vitamin D levels are linked to worse mood and cognitive performance in older adults, but more research is needed to prove whether improving vitamin D levels can actually improve brain health.
SCIENTIFIC POWER: MODERATE - The study uses solid testing methods and addresses an important issue, but its observational design and small sample limit the strength of its conclusions.
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