Why Are Vitamins Important for Your Brain?

Post by Meagan Marks

Nutrition and brain health

What you eat plays a crucial role in brain physiology and function and influences mood and mental health. Proper intake of micronutrients is vital for neurological and psychiatric well-being, with inadequate micronutrient levels potentially leading to problems with stress, hormone regulation, sleep, and overall cognitive function. 

What are vitamins?

Vitamins are essential organic compounds that our bodies need to function properly. The human body cannot make most vitamins on its own, so we must get them from our diet. When it comes to the brain, vitamins help maintain optimal psychiatric and neurological health by performing key functions: neurotransmitter synthesis, neuron growth, and neurochemical balance regulation. Particularly important, vitamins help protect against excitotoxicity, oxidative stress, and neuroinflammation – three main drivers of psychiatric and neurological disease.

Despite their importance, vitamin deficiencies are surprisingly common, particularly in the United States where the prevalent Western diet is highly processed and often lacking in micronutrients. In fact, it’s been suggested that this rise in micronutrient deficiency may be one factor related to the rise of mental and neurological disorders seen in the US.

So, which vitamins are indispensable for neurological functioning? How do they function in the brain? What risks come with deficiency, and what are some easily accessible food sources to add to your diet?

Vitamin A

Vitamin A is most known for its role in neurodevelopment and synaptic plasticity. It interacts with receptors in the brain that regulate the expression of genes that are involved in the formation of new neurons and neural connections. This is essential for learning, memory, and recovery from brain injuries. In addition, vitamin A also holds antioxidant properties that help protect the brain against oxidative stress and damage.

Adequate vitamin A levels are associated with better cognitive function, while deficiencies have been linked to cognitive impairments and increased risk of neurodegenerative disease. Food sources high in vitamin A include mangos, papayas, leafy vegetables, milk, eggs, and cheese. A note of caution, however: too much vitamin A (typically via oversupplementation) can be toxic!

B Vitamins

The B vitamins are a group of eight vitamins that perform some of the most essential and interconnected roles in the brain. B vitamins predominantly act as coenzymes, fusing with numerous proteins to boost their potential and help them perform more chemical reactions. Most notably, the B vitamins are responsible for synthesizing neurotransmitters and other signaling molecules in the brain.

Specific examples of their functions include:

B1 (thiamine) synthesizes precursors to neurotransmitters and other compounds essential to neuron function and structure. This includes acetylcholine, a neurotransmitter important to memory, learning, arousal, and attention.

B2 (riboflavin) acts as an antioxidant and helps regulate thyroid hormones that are essential to metabolism. B2 also helps to form B6, an extremely important B vitamin listed below.

B3 (niacin) also holds antioxidant properties, as well as helps with DNA metabolism and repair, cellular signaling, and oxidative reactions.

B5 (pantothenic acid) aids in neuron communication by myelinating axons and contributing to the structure of cells.

B6 is one of the most important vitamins to brain health. It is required to make the “feel good” neurotransmitters dopamine and serotonin, as well as the inhibitory neurotransmitter GABA. With even a mild B6 deficiency, levels of these neurotransmitters can drop in the brain. This leads to an excess of the excitatory neurotransmitter glutamate, which is linked to anxiety, depression, and excitotoxicity.

B8 (folic acid) and B12 are also both important to neurotransmitter synthesis, while B7 (biotin) is important for glucose metabolism.

Deficiencies in any of these vitamins will alter the brain’s ability to produce energy and perform essential processes, which can lead to chronic disease, psychiatric illness, and cognitive decline. Insufficient intake can manifest in many forms, including irritability, disordered sleep, inflammation, dementia, depression, and mental fog. Good sources of the B vitamins include fish, nuts, brown rice, pasta, citrus fruits, and leafy greens. 

Vitamin C

Vitamin C enhances neuron communication by myelinating axons, wrapping them in a protective, lipid-rich blanket. It also acts as a cofactor in producing dopamine and norepinephrine, neurotransmitters essential for motivation, mood, sleep, attention, and stress. Vitamin C is also a strong antioxidant, protects against excitotoxicity, and reduces inflammation by removing the proteins that cause it.

Deficiencies in vitamin C can lead to neuroinflammation, excitotoxicity, and oxidative stress, and may manifest as fatigue, mood swings, irritability, and depression. Great sources include bell peppers, citrus fruits, and various greens and vegetables.

Vitamin D

Vitamin D is well-known for managing fetal neurodevelopment and dopamine regulation. During pregnancy, vitamin D deficiency has been linked to abnormal neurodevelopment and is associated with an increased risk of schizophrenia and autism, which is thought to be due to impacts on dopamine regulation. Vitamin D supports the synthesis, transportation, and release of dopamine and is also positively correlated with growth and population of dopaminergic neurons.

Having a deficiency in vitamin D can increase the risk of cognitive decline, Alzheimer's disease, and Parkinson's disease and can greatly imbalance dopaminergic signaling. Great sources include fish, butter, cod liver oil, meat, milk, and eggs.

Vitamin E

Vitamin E is another vitamin that plays a strong protective role against oxidative stress, excitotoxicity, and neuroinflammation. Vitamin E can directly break down glutamate in the brain, reducing the risk of excitotoxicity and preventing cell damage. It also lowers levels of inflammatory proteins, reducing brain inflammation. Vitamin E also protects brain tissue by serving as an antioxidant.

Deficiencies may result in cognitive impairments, motor issues and muscle weakness. Good sources of vitamin E include seeds, nuts, avocados, sweet potatoes, and fish.

Vitamin K

While vitamin K is mostly known for its role in blood clotting and bone health, some emerging evidence suggests it also plays a role in brain function. Current findings suggest that it can reduce oxidative stress and neuroinflammation, help maintain cell membrane integrity, and support neuron survival and growth, but more research is needed to fully understand its role. Past studies have also shown that sufficient levels of vitamin K may improve cognitive performance and slow cognitive decline. 

Deficiencies may result in fatigue, irritability, and sleep disturbances, and great sources include leafy greens, vegetable oils, fruits, meat, eggs, and soybeans. 

What’s the takeaway?

Proper nutrition is essential to optimal neurological and psychiatric functioning. Consuming proper levels of micronutrients, whether through diet alone or with the help of supplementation under medical supervision, has been shown to 1) reduce stress, anxiety, and depression, 2) protect against inflammation, oxidative stress, and excitotoxicity, and 3) improve memory and cognitive tasks. While nutritional neuroscience is still a growing field, there is evidence that a proper and personalized diet could help prevent, manage, or even treat neurological and psychiatric disorders.

Access topic overview citations here: 1, 2, 3, 4, 5, 6, and 7.

Gene Variants Predicting Stroke Recovery Outcomes

Post by Natalia Ladyka-Wojcik

The takeaway

For stroke survivors, factors such as age, baseline health, and stroke severity have been highlighted as important when predicting recovery outcomes, but a key factor – genetics – has received much less attention to date. Yet, there may be specific gene variants that can help to predict the cognitive and emotional trajectories of recovery for stroke survivors, providing instrumental insights into future therapeutic approaches. 

What's the science?

The outcomes of stroke are long-term, with patients often experiencing a range of cognitive and emotional changes that impact quality of life. A wealth of previous research has investigated genetic factors associated with stroke risk and severity, but there has been considerably less exploration into genetic associations with stroke recovery. Although treatments for stroke patients are becoming more targeted, including the promotion of neural repair, we still understand very little in terms of how genetics may interact with the success of these treatments. Importantly, in order to link specific genetic variants to post-stroke outcomes, researchers also need to identify ways of measuring these outcomes beyond a single index of global disability. This week in Stroke, Cramer and colleagues analyzed three candidate gene variants to determine their potential associations with a series of key motor and functional measures in stroke recovery.

How did they do it?

The authors analyzed genetic data and recovery outcomes from a large-scale, prospective cohort study called STRONG (Stroke, sTress, RehabilitatiON, and Genetics) including more than 750 adult patients with stroke across 28 US stroke centers. Specifically, they examined patients for a period of 1-year post-stroke, to identify genetic variants associated with motor and functional outcomes, as well as stress-related outcomes. At the initial timepoint of the study, the authors collected saliva samples for DNA genotyping analysis. This DNA analysis considered the genetic ancestry of patients, and candidate gene variants were selected based on prior research linking them to specific motor, functional, or stress-related outcomes. For motor and functional outcomes, they selected ApoE ε4 carrier status and brain-derived neurotrophic factor (BDNF) polymorphism, which have both been tied to reduced neural repair in past research. They also selected a dopamine polygenic score (i.e., a characteristic influenced by two or more genes) which models the neurotransmission of dopamine in the human brain. Together, these selected gene variants were analyzed in terms of their predictive relationship to longitudinal outcomes in grip strength, global functional daily living, depression, and cognitive status. Finally, for stress-related outcomes, the authors investigated seven additional gene variants in relation to post-traumatic stress disorder (PTSD) and depression across several timepoints of the longitudinal study. To bolster their results, the authors considered stroke subtypes (which can vary in their symptoms and underlying causes) and also conducted a replication analysis to compare their results to two other previously published, large-scale cohort studies. 

What did they find?

For functional outcomes, the authors found that BDNF polymorphism was associated with poorer cognition in stroke patients, as well as reduced grip strength when considering the time from stroke onset to study enrollment. APOE status and dopamine polygenic scores were not found to be related to their measured outcomes, further highlighting the precision with which targeted therapies need to consider whether or not a gene factors into stroke recovery. For stress-related outcomes, the authors identified two of the seven gene variants contributed to poorer outcomes in terms of PTSD and depression, while another one contributed to better outcomes in terms of PTSD and depression. Importantly, stress-related gene variants also broadly varied with the level of post-stroke stress experienced by patients. These genetic associations were found to be important regardless of stroke subtype and most critically, were only evident at 1-year post-stroke but not earlier. As the authors point out, this is why it is important to consider genetic variants not just at the initial stages of recovery but rather in the long term. Finally, their findings successfully replicated results from another large-scale genetic study of post-stroke outcomes, with a genetic variant involved in the expression of a protein associated with brain plasticity predicting global post-stroke outcomes in both studies. 

What's the impact?

This study found that comprehensive genetic phenotyping after stroke holds key insights into predicting long-term outcomes for patients. Notably, this study provides a deeper understanding of post-stroke recovery than mere global outcomes scores, by measuring specific functional, motor, and stress-related outcomes and also by considering how much stress the patients reported experiencing. Altogether, these insights could help develop future tailored therapies for patients and potentially identify patients who may need more support to achieve better post-stroke recovery based on genetic risk.  

Access the original scientific publication here.

What is Cognitive Reserve, Actually?

Post by Anastasia Sares

The takeaway

Cognitive function tends to decline as we age normally or when we are faced with diseases like Alzheimer’s. Cognitive reserve is a form of resilience that allows people to maintain good cognitive functioning—or at least to slow cognitive decline—even as aging and illness progress.

The idea of cognitive reserve

Studies of aging have noted large individual differences in rates of cognitive decline, whether it be in healthy aging or dementias like Alzheimer’s. Cognitive reserve is a concept scientists have proposed to account for this variability. Things like education and occupational complexity may contribute to cognitive reserve, with one study finding that high cognitive reserve reduced the risk of dementia by around 50%. However, to move the research forward, researchers need to first agree on how to define cognitive reserve. Over the past several years there has been an effort to do just that. In this article, we will present the definitions of Stern and colleagues, who are leaders in this field.

Three necessary elements

To show evidence of cognitive reserve at work, you need three elements. First, you need some kind of outcome measure: for example, the presence or absence of an Alzheimer’s diagnosis, or a score on a cognitive test. Second, you need some kind of risk factor. Often, this is brain-related, like the number of accumulated protein plaques or the integrity of white matter in the brain. But the risk factor doesn’t have to be from the brain: for example, a person’s age is, by itself, a risk factor for Alzheimer’s. These first two elements (the outcome and the risk factor) are assumed to have a causal relationship. For example, more plaques in the brain should lead to a greater likelihood of an Alzheimer’s diagnosis.

The third element is where it gets interesting. This is a protective factor that we think might moderate the relationship between the first two elements. For example, perhaps people who have more education can maintain their cognitive functioning for longer and delay their Alzheimer’s diagnosis compared to people with the same number of plaques in their brain but less education. Or perhaps people who are more socially active score higher on cognitive tests for their age than people who are less socially active.

Related concepts

There are a couple of concepts related to cognitive reserve, but slightly different. To differentiate these terms, a hardware/software analogy is sometimes used. Cognitive reserve is the “software” that allows for maintained function despite deteriorating “hardware,” while brain reserve is the pre-existing advantages in the biological “hardware” itself. For example, in a study looking at white matter integrity changes with age, you might find that some individuals just have better white matter integrity, to begin with, before any aging or disease. This means it will take more damage to the white matter to start affecting cognition. The hardware/software analogy is imperfect, and the line between cognitive reserve and brain reserve is fuzzy. After all, cognitive processes are also based in biology.

Brain maintenance, on the other hand, involves stalling the damage to the brain’s “hardware” so that the decline is not so sharp. For example, some people may accumulate white matter damage at a slower rate than others.

All of these elements are most informative when measured longitudinally (using multiple measurements over time), so long-term changes can be tracked. This would allow researchers to pick apart differences between cognitive reserve, brain reserve, and brain maintenance, where a single snapshot might not.

What’s the impact?

Cognitive resilience in the face of aging is increasingly important as populations all over the world grow older on average. Having a consensus on the definition of cognitive reserve allows scientists to move forward studying it, potentially identifying ways to build it up and increase quality of life in old age.

References +

Cabeza, R., Albert, M., Belleville, S., Craik, F. I. M., Duarte, A., Grady, C. L., Lindenberger, U., Nyberg, L., Park, D. C., Reuter-Lorenz, P. A., Rugg, M. D., Steffener, J., & Rajah, M. N. (2018). Maintenance, reserve and compensation: The cognitive neuroscience of healthy ageing. Nature Reviews Neuroscience, 19(11), 701–710. https://doi.org/10.1038/s41583-018-0068-2

Stern, Y., Albert, M., Barnes, C. A., Cabeza, R., Pascual-Leone, A., & Rapp, P. R. (2023). A framework for concepts of reserve and resilience in aging. Neurobiology of Aging, 124, 100–103. https://doi.org/10.1016/j.neurobiolaging.2022.10.015

Stern, Y., Arenaza‐Urquijo, E. M., Bartrés‐Faz, D., Belleville, S., Cantilon, M., Chetelat, G., Ewers, M., Franzmeier, N., Kempermann, G., Kremen, W. S., Okonkwo, O., Scarmeas, N., Soldan, A., Udeh‐Momoh, C., Valenzuela, M., Vemuri, P., Vuoksimaa, E., & and the Reserve, Resilience and Protective Factors PIA Empirical Definitions and Conceptual Frameworks Workgroup. (2020). Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimer’s & Dementia, 16(9), 1305–1311. https://doi.org/10.1016/j.jalz.2018.07.219

Nelson, M. E., Jester, D. J., Petkus, A. J., & Andel, R. (2021). Cognitive Reserve, Alzheimer’s Neuropathology, and Risk of Dementia: A Systematic Review and Meta-Analysis. Neuropsychology Review, 31(2), 233–250. https://doi.org/10.1007/s11065-021-09478-4