Health and Medicine
Exploring the influence of vitamin D on the human brain

Exploring the influence of vitamin D on the human brain

Summary

  • Vitamin D, obtained mainly through sun exposure or dietary sources, is crucial for bone integrity, muscle health, and immune function.
  • Maternal vitamin D deficiency has been linked to neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder.
  • Vitamin D plays a vital role throughout life with its anti-inflammatory, antioxidant, and other neuroprotective properties.
  • Vitamin D receptors are especially present in brain areas relating to cognition and emotion regulation, possibly explaining the influence that vitamin D deficiency plays on related disorders.
  • Studies suggest a complex relationship between vitamin D and depression, with mixed results on the efficacy of supplementation, emphasizing the need for further investigation into this area.

Vitamin D, often referred to as the “sunshine vitamin”, is obtained through sun exposure and dietary sources such as fatty fish and egg yolks [1,2]. Vitamin D can also be taken in through dietary supplements, a topic discussed in more detail in this past article. The importance of vitamin D for bone integrity, muscle health, and the immune system has long been established [3]. But besides that, does vitamin D play any role in our brain? And if so, how does lack thereof affect us? In a world where vitamin D deficiency is more prevalent than ever, such questions need to be addressed. Vitamin D deficiency currently affects a population of 1 billion individuals worldwide [4]. This deficiency can for example be attributed to less sun exposure (more time indoors), increased use of sunscreen, less physical activity, and poor socioeconomic background [5]. This article delves into the role of vitamin D and its impact on the human brain, exploring emerging research on its implications for brain function and development.

Nearly two decades ago, researchers discovered that vitamin D receptors are widely distributed through the human brain, mirroring the patterns seen in rodents [6]. This allowed the investigation of vitamin D’s role as a “neuroactive steroid”, a compound that can quickly exert a change to a neuron’s behavior by interacting directly with its receptors. Specifically, vitamin D has been shown to affect neuronal cell differentiation (helping neurons mature correctly), neurotransmitter synthesis (the messenger in our brain), calcium signaling (helping neurons communicate with one another), as well as creating genes and proteins important for brain structure and function [6]. Considering the importance of vitamin D on various neuronal functions, vitamin D deficiency is expected to exert a number of disruptions. Let’s have a closer look at several scientific studies.

Vitamin D has been found to play a crucial role during brain development, already before birth [7]. Lack of vitamin D in pregnant women has been linked to a higher risk of certain neurodevelopmental disorders, such as schizophrenia, in their children [8]. Curiously, the very season in which a person is born can impact their risk for schizophrenia, with those born in the winter and spring months facing a slightly elevated risk – a phenomenon partly attributed to reduced sunlight exposure [9,10]. This has been shown through both animal and human epidemiological studies [10]. For example, an experimental study looked at the influence of prenatal (before birth) vitamin D deficiency on the brains of mice [11]. They found that lack of vitamin D resulted in larger brains with a thinner neocortex compared to the brains of the control mice. This change was due to increased cell proliferation (growth), as well as a deficient apoptosis process, which is a crucial phenomenon during gestation that eliminates unwanted neurons. Neuronal apoptosis is a key event in mammalian brain development [12]. It is important to keep in mind that this is a rodent study and not a human study. Although the pattern of vitamin D receptors in the human brain has been reported to be strikingly similar to that of rodents, any generalizations from rodents to humans need to be approached with precautions [6]. This is especially the case because rodents are nocturnal animals and their vitamin D needs may vary from that of humans.

As for human epidemiological studies, a systematic review compared maternal vitamin D levels during pregnancy with the psychiatric outcomes of the children [13]. 29 studies were included in this review, including data from various countries in Europe, Australia, China, and the USA. This systematic review finds an association between maternal vitamin D deficiency and autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia diagnoses. Furthermore, more positive associations between maternal vitamin D deficiency and psychiatric outcomes were found in northern European countries, countries known to have little sunlight in the winter months. This systematic review however reports several limitations, such as some studies not accounting for the mothers’ psychiatric background or small sample sizes. Furthermore, these are observational associations and therefore no definite conclusions can be drawn regarding the causality of these data.

Even after the brain is fully developed, vitamin D continues to play a crucial role in maintaining brain health. It has been found to induce anti-inflammatory and antioxidant properties, which may help reduce negative effects such as neurodegeneration (death of neurons) and impaired neurotransmission (communication between neurons) [14,15]. Moreover, studies have shown that vitamin D supplementation can offer neuroprotective benefits, potentially slowing cognitive decline associated with dementia [16,17]. Especially older populations are affected by vitamin D deficiency because their body is less able to synthesize vitamin D from the resources available [15,18]. A meta-analysis (a large study collecting information from several studies) conducted in 2024 looked at the relationship between vitamin D deficiency and risk for dementia [19]. They found that vitamin D deficiency was a risk factor for dementia, Alzheimer’s disorder, and cognitive impairment [19]. This suggests that optimal vitamin D levels may promote healthy brain aging [18]. However, studies that looked at vitamin D supplementation in participants who already had Alzheimer’s disease do not find sufficient evidence indicating that this may help improve cognitive functioning in Alzheimer’s [20]. Vitamin D supplementation seems to exert very different effects on dementia prevention as compared to relieving symptoms.

Vitamin D receptors have been found to be particularly present in brain areas essential for cognition and emotional regulation, such as the temporal, cingulate, and orbital cortex [21]. Considering the associations found between vitamin D and disorders such as schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder, and dementia – all disorders where cognition comes into play – vitamin D does indeed seem to play a crucial role in cognitive brain functions [18].

Lastly, the relationship between vitamin D and mood regulation, particularly in the context of depression, has also been explored [22]. While cross-sectional studies (looking at a population at a specific point in time) have suggested a link between lower vitamin D levels and depression, the causality of this relationship remains unclear. For example, when looking at this association in regard to different factors such as demographics, geographical location, gender, smoking status, or age, the strength of this association appears to fluctuate [22]. Attempts to alleviate depressive symptoms through vitamin D supplementation also yielded mixed results [22]. If and how vitamin D and depression interact therefore remains unclear and needs further investigation.

In conclusion, the above-mentioned findings highlight the multifaceted role of vitamin D on brain health, from its significance during development to its potential neuroprotective role in cognition and mood-regulating effects. As vitamin D deficiency remains a widespread issue, understanding its impact on brain functioning is crucial in order to address it accurately – in regard to psychiatric disorders, as well as to our overall well-being.

References:

  1. Borji, S., & Rafieian-kopaei, M. (2015). Vitamin D and its importance on public health. Journal of Parathyroid Disease, 4, 20-24.
  2. McGee M. (2020). Vitamin D: Insufficiency, Uncertainty and Achievability. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, 90(1-2), 1–4. https://doi.org/10.1024/0300-9831/a000500
  3. Janoušek, J., Pilařová, V., Macáková, K., Nomura, A., Veiga-Matos, J., Silva, D. D. D., Remião, F., Saso, L., Malá-Ládová, K., Malý, J., Nováková, L., & Mladěnka, P. (2022). Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites. Critical reviews in clinical laboratory sciences, 59(8), 517–554. https://doi.org/10.1080/10408363.2022.2070595
  4. Sizar, O., Khare, S., Goyal, A., & Givler, A. (2023). Vitamin D Deficiency. In StatPearls. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532266/
  5. Lips, P., de Jongh, R. T., & van Schoor, N. M. (2021). Trends in Vitamin D Status Around the World. JBMR plus, 5(12), e10585. https://doi.org/10.1002/jbm4.10585
  6. Eyles, D. W., Smith, S., Kinobe, R., Hewison, M., & McGrath, J. J. (2005). Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. Journal of chemical neuroanatomy, 29(1), 21–30. https://doi.org/10.1016/j.jchemneu.2004.08.006
  7. Eyles D. W. (2020). Vitamin D: Brain and Behavior. JBMR plus, 5(1), e10419. https://doi.org/10.1002/jbm4.10419
  8. Samoes, B., & Silveira, C. (2018). The role of vitamin D in the pathophysiology of schizophrenia. Neuropsychiatry, 07(04). https://doi.org/10.4172/neuropsychiatry.1000223
  9. Alvarez-Mon, M. A., Guillen-Aguinaga, S., Pereira-Sanchez, V., Onambele, L., Al-Rahamneh, M. J., Brugos-Larumbe, A., Guillen-Grima, F., & Ortuño, F. (2021). Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain. Journal of clinical medicine, 10(13), 2859. https://doi.org/10.3390/jcm10132859
  10. McGrath, J. J., Burne, T. H., Féron, F., Mackay-Sim, A., & Eyles, D. W. (2010). Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophrenia bulletin, 36(6), 1073–1078. https://doi.org/10.1093/schbul/sbq101
  11. Groves, N. J., Zhou, M., Jhaveri, D. J., McGrath, J. J., & Burne, T. H. J. (2017). Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice. Psychoneuroendocrinology, 86, 53–63. https://doi.org/10.1016/j.psyneuen.2017.09.003
  12. Blanquie, O., Kilb, W., Sinning, A., & Luhmann, H. J. (2017). Homeostatic interplay between electrical activity and neuronal apoptosis in the developing neocortex. Neuroscience, 358, 190–200. https://doi.org/10.1016/j.neuroscience.2017.06.030
  13. Upadhyaya, S., Ståhlberg, T., Silwal, S., Arrhenius, B., & Sourander, A. (2022). Maternal Vitamin D Levels during Pregnancy and Offspring Psychiatric Outcomes: A Systematic Review. International journal of molecular sciences, 24(1), 63. https://doi.org/10.3390/ijms24010063
  14. Lisi, G., Ribolsi, M., Siracusano, A., & Niolu, C. (2020). Maternal Vitamin D and its Role in Determining Fetal Origins of Mental Health. Current pharmaceutical design, 26(21), 2497–2509. https://doi.org/10.2174/1381612826666200506093858
  15. Anjum, I., Jaffery, S. S., Fayyaz, M., Samoo, Z., & Anjum, S. (2018). The Role of Vitamin D in Brain Health: A Mini Literature Review. Cureus, 10(7), e2960. https://doi.org/10.7759/cureus.2960
  16. Annweiler C. (2016). Vitamin D in dementia prevention. Annals of the New York Academy of Sciences, 1367(1), 57–63. https://doi.org/10.1111/nyas.13058
  17. Lau, H., Mat Ludin, A. F., Rajab, N. F., & Shahar, S. (2017). Identification of Neuroprotective Factors Associated with Successful Ageing and Risk of Cognitive Impairment among Malaysia Older Adults. Current gerontology and geriatrics research, 2017, 4218756. https://doi.org/10.1155/2017/4218756
  18. Latimer, C. S., Brewer, L. D., Searcy, J. L., Chen, K. C., Popović, J., Kraner, S. D., Thibault, O., Blalock, E. M., Landfield, P. W., & Porter, N. M. (2014). Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proceedings of the National Academy of Sciences of the United States of America, 111(41), E4359–E4366. https://doi.org/10.1073/pnas.1404477111
  19. Zhang, X. X., Wang, H. R., Meng-Wei, Hu, Y. Z., Sun, H. M., Feng, Y. X., & Jia, J. J. (2024). Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies. Journal of Alzheimer’s disease : JAD, 98(2), 373–385. https://doi.org/10.3233/JAD-231381
  20. Chakkera, M., Ravi, N., Ramaraju, R., Vats, A., Nair, A. R., Bandhu, A. K., Koirala, D., Pallapothu, M. R., Quintana Mariñez, M. G., & Khan, S. (2022). The Efficacy of Vitamin D Supplementation in Patients With Alzheimer’s Disease in Preventing Cognitive Decline: A Systematic Review. Cureus, 14(11), e31710. https://doi.org/10.7759/cureus.31710
  21. Gáll, Z., & Székely, O. (2021). Role of Vitamin D in Cognitive Dysfunction: New Molecular Concepts and Discrepancies between Animal and Human Findings. Nutrients, 13(11), 3672. https://doi.org/10.3390/nu13113672
  22. Menon, V., Kar, S. K., Suthar, N., & Nebhinani, N. (2020). Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions. Indian journal of psychological medicine, 42(1), 11–21. https://doi.org/10.4103/IJPSYM.IJPSYM_160_19