The Central Role of BDNF in Brain Health
BDNF (or Brain-derived neurotrophic factor) is one of the most important growth factors influencing brain development, growth, and formation of new neural connections (R). It also plays an important role in health, sleep (R), stress response (R), depression, anxiety (R), and even body weight (R). Today we will discuss why this is important and how to increase your levels of BDNF on a daily basis.
BDNF encodes a protein that plays an essential role in promoting the survival of nerve cells or neurons by aiding in their growth, maturation, and maintenance (R, R). BDNF also facilitates learning and memory by participating in synaptogenesis, the formation of synapses between neurons in the nervous system.
Despite its significant role in brain health and cognition, BDNF levels can vary considerably between individuals. These variances can be traced back to genetic factors that we'll explore in this blog post. Importantly, we'll also discuss practical strategies for increasing your BDNF levels.
The Science of BDNF
BDNF functions in the central and peripheral nervous systems, contributing to neurons' development, function, and survival. It achieves these effects through two main mechanisms:
Synaptic Plasticity
BDNF plays a crucial role in synaptic plasticity, which is the ability of synapses (the junctions between neurons) to strengthen or weaken over time. This adaptability is central to learning and memory formation (R). Higher levels of BDNF can promote the creation of new synapses, enhance the strength of existing synapses, and increase the survival of neurons, contributing to better cognitive function.
Neurogenesis
BDNF also promotes neurogenesis, the process of creating new neurons from neural stem cells. This process occurs throughout life, predominantly in the hippocampus, an area of the brain essential for learning and memory. By promoting neurogenesis, BDNF supports our brain's structure's continual renewal and adaptability (R).
Understanding BDNF's Genetic Blueprint
The BDNF Gene
The BDNF gene, responsible for producing the BDNF protein, is found in each human on chromosome 11. There is a key point of variation in this gene, known as the Val66Met polymorphism (rs6265 variant). Some individuals have the 'Val' variant, others have the 'Met' variant, and these genetic differences can influence the level of BDNF protein that a person's cells can produce. You can find out your BDNF status by looking at your 23andme data (search for rs6265 under raw data). Remember that this variant is one of many genetic associations that affect your health outcomes. And it is just an association, not a direct cause and effect.
Early studies have associated the ‘C/C’ (“val”) allele with relatively higher levels of BDNF, while the ‘T/T’ (“met”) allele has been linked to relatively lower levels or production of BDNF (R, R). (Note this may vary between different ethnic groups)
Because everyone has two copies of each gene – one from their mother and one from their father – each person has two copies (or two) alleles for this SNP. This means there are a total of three different genotypes, that a person can have:
CC (Val) = homozygous major
CT (Val/Met’ = heterozygous
TT (Met) = homozygous minor
BDNF Gene and Mental Health
Research has shown that individuals with the 'Met' variant of the BDNF gene may have a reduced ability to transport the BDNF protein to where it is needed, which can lead to lower overall BDNF levels. Several studies have linked this variant to a higher risk of mental health disorders like depression and schizophrenia (R). However, it's important to note that having the 'Met' variant doesn't guarantee the onset of these disorders. Environmental factors and other genes also play crucial roles in shaping our mental health.
BDNF and Weight
BDNF is expressed in our hypothalamus (R), the control center for hunger and satiety signals, where it directly influences our eating behaviors. Research shows that lower levels of BDNF can increase appetite, leading to overeating and subsequent weight gain (R, R)). Conversely, higher levels of BDNF can suppress appetite and contribute to weight loss (R).
Studies show that individuals with obesity tend to have lower BDNF levels (R), indicating a vicious cycle where weight gain and reduced BDNF reinforce each other. This scenario underscores the delicate balance that needs to be maintained, drawing attention to BDNF's critical role in weight regulation.
Furthermore, the effect of BDNF isn't limited to just appetite regulation. BDNF also plays a role in energy metabolism (R). It is believed to enhance the body's fat utilization, thereby contributing to weight management.
Understanding BDNF's role in weight management carries significant implications. It means we can impact our weight by influencing our BDNF levels. So how can we turn up the dial on our BDNF production? Keep reading to find out.
BDNF and Sleep
How does BDNF relate to sleep, you may wonder? Research over the past years has shown that there's a significant relationship between sleep and BDNF levels. Our sleep architecture, comprising REM (rapid eye movement) and non-REM sleep, influences and is influenced by BDNF in a bidirectional relationship (R).
BDNF levels have been found to fluctuate in sync with our circadian rhythms, peaking during the day and dropping at night (R). Studies show that non-REM sleep, particularly slow-wave sleep, increases BDNF expression, thus promoting synaptic plasticity and memory consolidation.
On the flip side, disruptions to sleep, such as sleep deprivation, decrease BDNF levels (R). This reduction might explain why insufficient sleep often results in cognitive impairments and mood disruptions. In extreme cases, chronic sleep disturbances have been linked with neurodegenerative diseases like Alzheimer's, where BDNF deficits are commonly observed (R).
Now that we understand the dance between BDNF and sleep, weight, and mental health, it becomes clear that ensuring their harmony is crucial. So, how can we apply this knowledge to optimize our BDNF function? Let's dive into that next.
Top 10 Natural Methods to Amplify BDNF Production
Despite genetic variations, there are several ways to boost the production of BDNF naturally.
1. Regular Physical Exercise Regular physical exercise is a potent BDNF booster (R). Whether it's a brisk walk in the park, an invigorating swim, or a high-intensity interval training session, regular physical activity can help enhance BDNF levels, thereby supporting appetite control and healthy weight management. Exercise also boosts long-term memory through BDNF (R).
2. A Healthy Anti-Inflammatory Diet Diet, too, plays a role. Consuming a balanced diet rich in omega-3 fatty acids, antioxidants, and other nutrients can stimulate BDNF production (R, R, R). Moreover, calorie restriction has been found to increase BDNF levels (R). Eating a diet rich in fruits, vegetables, lean proteins, and omega-3 fatty acids can help promote BDNF production and, in doing so, improves neural plasticity (R). On the other hand, diets high in processed and sugary foods may reduce BDNF levels.
Foods That Increase BDNF:
Omega-3 Rich Foods Foods like fatty fish (e.g., salmon, mackerel), chia seeds, and walnuts, which are rich in omega-3 fatty acids, can increase BDNF levels (R, R).
Berries Berries, including blueberries, strawberries, and blackberries, contain antioxidants and other compounds that can increase BDNF levels and may improve memory (R, R, R)
Green Tea As mentioned earlier, green tea contains EGCG, which boosts BDNF levels (R).
Turmeric Curcumin in turmeric increases BDNF production, which increases the growth of new neurons and may help fight degenerative processes in the brain (R, R).
3. Intermittent Fasting Fasting, or the restriction of caloric intake for specific periods, has been found in several studies to upregulate the expression of BDNF (R, R). But why and how does this occur?
The body's response to fasting is complex and multifaceted, and it involves several metabolic adjustments to preserve energy and maintain vital physiological functions. When we fast, our bodies shift from utilizing glucose as a primary source of energy to burning fat. This metabolic switch triggers the production of ketones, molecules that serve as alternative energy sources for the body and the brain during periods of low glucose availability.
One particular ketone body, beta-hydroxybutyrate (BHB), plays a key role in the fasting-induced upregulation of BDNF (R, R). BHB can cross the blood-brain barrier (R) and has been found to enhance BDNF expression in the brain (R). This is partly due to BHB's ability to inhibit enzymes called histone deacetylases (R), leading to changes in the DNA structure that enable the increased expression of specific genes, including the BDNF gene (R).
Additionally, fasting stimulates the production of various protective proteins and enhances mitochondrial health, increasing neuronal resistance to stress and injury. These processes, too, are linked with elevated BDNF levels.
Fasting also indirectly influences BDNF levels by impacting several physiological variables, such as reducing inflammation and improving insulin sensitivity, which could increase BDNF expression.
The upregulation of BDNF during fasting, thus, appears to be an adaptive response that helps the brain cope with the metabolic challenge. Increased BDNF levels promote neuroplasticity, support cognitive function, and protect the brain against stress, making this upregulation a key part of the brain's response to fasting.
4. Cognitive Challenges Engaging in cognitive challenges, such as solving puzzles, learning new skills, or participating in intellectual tasks, can help to boost the production and expression of brain-derived neurotrophic factor (BDNF), a crucial protein that promotes brain health (R).
Cognitive challenges act as a form of mental exercise. Just as physical exercise strengthens our muscles, mental exercises stimulate and strengthen our brains. Engaging our brain in challenging tasks triggers a process known as neuroplasticity – the brain's ability to form and reorganize synaptic connections, especially in response to learning or experience. BDNF plays a critical role in this process.
Engaging in complex cognitive tasks essentially stimulates our neurons to grow, adapt, and form new connections. As this happens, the brain responds by increasing the production of BDNF to support these changes. Moreover, studies have shown that these cognitive challenges do not just increase BDNF levels temporarily. With consistent mental exercise, the brain adapts by enhancing the overall expression of BDNF over time. This increased BDNF expression can lead to long-term improvements in cognitive function, memory, and resilience against brain-related disorders.
5. Carbohydrate Restriction (occasional)
Carbs are important for gut health, hormone balance, energy, and sleep, amongst other things. I would never advise cutting them out completely. However, strategic bouts of carbohydrate restriction, such as ketogenic diets or intermittent fasting, can significantly impact brain-derived neurotrophic factor (BDNF) expression (R, R). As with fasting, when carbohydrate intake is limited, the body switches from using glucose as its primary energy source to using fats or ketones.
As we learned with fasting, one specific ketone body, BHB, plays a key role in the upregulation of BDNF. Recall this leads to changes in the epigenetics or expression of the BDNF gene, altering its function.
Carbohydrate restriction also can lead to a state of mild cellular stress, similar to the stress caused by exercise or fasting. In response to this, cells increase the production of various protective proteins, including BDNF, to combat stress. This phenomenon is part of what's known as hormesis – the process by which moderate stress leads to increased resistance to damage and enhanced longevity.
Additionally, carbohydrate restriction can lead to improved insulin sensitivity. Since insulin resistance and chronically high insulin levels have been linked with reduced BDNF levels, improving insulin sensitivity can potentially contribute to higher BDNF expression.
6. Infrared Sauna & Cold Plunge
Infrared sauna and cold plunge, two contrasting yet equally stimulating environmental stressors, can affect the expression and function of brain-derived neurotrophic factor (BDNF) in fascinating ways.
Infrared saunas emit wavelengths of light absorbed by the body's cells, causing a gentle increase in body temperature. This induced hyperthermia is a form of stress, but like exercise, it's a 'good' type of stress that can lead to hormesis (R). This is where moderate stress increases the body's resistance to damage and stimulates the production of beneficial proteins - including BDNF (R). Regular infrared sauna use can potentially increase BDNF levels, which in turn helps support the growth and survival of neurons, facilitates synaptic plasticity, and boosts overall brain health.
Moreover, the heat stress induced by infrared saunas leads to the release of 'heat shock proteins', which have protective effects on cells and have been found to interact with BDNF pathways to promote neuroplasticity and cognitive function (R).
On the other end of the spectrum, the cold plunge or cold exposure similarly induces a stress response but through a different mechanism. Cold exposure stimulates the production of norepinephrine, a neurotransmitter that is released in response to stress and has been shown to enhance the expression of BDNF. The sudden exposure to cold also triggers a process called cold-shock response, including upregulating cold-shock proteins (R). One of these proteins, RNA-binding motif protein 3 (RBM3), is thought to potentially interact with BDNF pathways to promote synaptic plasticity and neuroprotection (R).
The contrasting stimuli of infrared sauna and cold plunge may provide a unique form of environmental enrichment, stimulating BDNF production and function from different angles and potentially leading to improved brain health and cognitive function.
7. Adequate Sleep Getting enough quality sleep can also boost BDNF levels. Sleep disorders and deprivation have been linked to reduced BDNF levels. Adhering to good sleep hygiene - maintaining a consistent sleep schedule, ensuring a sleep-friendly environment, and avoiding sleep-disrupting habits - helps stabilize our circadian rhythms, thus supporting optimal BDNF function. When our sleep patterns are regular and restful, BDNF levels are naturally boosted, benefiting cognitive functions, mood, and overall brain health.
On the other hand, poor sleep hygiene leads to disruptions in sleep, can decrease BDNF levels, impair cognitive abilities, and disrupt mood regulation. Therefore, good sleep hygiene is crucial for a good night's sleep and maintaining healthy BDNF levels and promoting overall brain health.
8. Mindfulness Practices Mindfulness practices, such as meditation and yoga, have been linked to the upregulation of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in brain health (R).
Mindfulness involves directing attention to one's experiences in the present moment non-judgmentally. Engaging in such practices can elicit a relaxation response, a physiological state of deep rest that changes the physical and emotional responses to stress.
This relaxation response can lead to a reduction in cortisol, the body's primary stress hormone. High cortisol levels have been associated with decreased BDNF expression, so by reducing cortisol, mindfulness practices can create an environment more conducive to BDNF production (R).
Moreover, mindfulness practices can stimulate various areas of the brain, including those involved in regulating emotions and cognitive functions. Regularly stimulating these areas through mindfulness practice can promote neuroplasticity – the brain's ability to reorganize itself by forming new neural connections. BDNF plays a critical role in this process; thus, its production is enhanced to support these changes.
Research has also shown that regular mindfulness practices can increase gray matter density in the brain regions associated with learning, memory, and emotion regulation. These structural changes correlated with higher BDNF levels, indicating a potential mechanism by which mindfulness could upregulate BDNF expression.
9. Sunlight Exposure Sunlight exposure, especially its blue light component, is key in enhancing the production of brain-derived neurotrophic factor (BDNF) (R). This process begins when sunlight enters the eye, stimulating specialized cells in the retina called intrinsically photosensitive retinal ganglion cells (ipRGCs), sending signals to various parts of the brain, including the hypothalamus (R).
Upon reaching the hypothalamus, these signals influence the suprachiasmatic nucleus (SCN), our circadian pacemaker. The SCN orchestrates the release of various hormones and neurotransmitters, including serotonin, which sees an increase upon sunlight exposure (R). Higher serotonin levels, in turn, have been associated with increased BDNF expression, benefiting neuronal health, mood, and cognition.
In addition to this, sunlight exposure aids the skin in synthesizing Vitamin D. Given that Vitamin D receptors are found in several brain regions and that this vitamin plays a role in BDNF production, sunlight-induced Vitamin D synthesis could indirectly support higher BDNF levels (R). In spring and summer, exposing the hands, face, neck, and arms to the sun for 8 to 10 minutes of sun exposure at noon produces the recommended amount of vitamin D. In the winter, it takes about 2 hours of exposure. However, it's crucial to balance the benefits of sunlight exposure with potential risks, such as skin damage, and individual factors should always be considered.
10. Social Interactions Positive social interactions significantly impact brain-derived neurotrophic factor (BDNF), a protein essential for brain health (R).
Social interaction, particularly when positive and meaningful, stimulates various areas of the brain related to reward, empathy, and emotional regulation. This stimulation promotes neuroplasticity - the brain's ability to reorganize itself by forming new neural connections. BDNF plays a critical role in this process, as it supports the growth and survival of neurons, facilitates synaptic plasticity, and thus its production is enhanced to support these changes.
Moreover, positive social interactions can reduce stress and anxiety levels. High levels of stress and anxiety have been linked with decreased BDNF expression. Therefore, social interaction creates a physiological environment more conducive to BDNF production by mitigating these stress responses.
Research has shown that individuals with a rich social life, strong social support, and frequent positive social interactions tend to have higher BDNF levels. This has been associated with improved mood, cognitive performance, and overall mental health. This was even associated with a reduced risk of stroke and dementia- so sign up for that book club or pickleball team.
However, the impact of social interaction on BDNF can vary based on the quality and nature of the interactions. Positive, supportive, and fulfilling social connections are key to deriving these benefits. In essence, maintaining positive social relationships is beneficial for emotional well-being and brain health, partly due to its role in enhancing BDNF expression.
Other Supplements That Support Healthy BDNF Levels Several supplements have been shown to increase BDNF levels:
Omega-3 Supplements: If your diet lacks omega-3-rich foods, consider omega-3 supplements like fish oil or algal oil (R).
Resveratrol: Resveratrol, a compound found in red wine, has been shown to increase BDNF levels. It can be taken as a supplement (R, R).
Probiotics: especially Lactobacillus and Bifidobacterium strains, can promote gut health, which has been linked to increased BDNF levels (R).
Rhodiola Rosea: is a natural adaptogen that has been shown to increase BDNF levels, improving depression, mood, and cognitive function (R).
L-theanine: Found in green tea, this amino acid works on glutamatergic receptors in the brain, producing a calming effect. One study found that L-theanine exerts an effect, in part, through the induction of BDNF in the hippocampus (R).
Green Tea: Multiple ingredients from green tea (EGCG- a natural catechin polyphenol, caffeine, and L-theanine) can boost BDNF and its effects on the brain. According to limited evidence, green tea extract rich in EGCG and caffeine may boost BDNF and slightly improve weight loss (R, R)
Magnesium: Magnesium supplementation increases the production of BDNF, with an effect on the central and peripheral nervous system, supports the survival, growth, and differentiation of neurons (R)
Resistant Starch: Resistant starch is food for the gut microbiome and facilities the production of short-chain fatty acids like butyrate by the gut microbes. Butyrate may support BDNF signaling in the brain (R). Get more butyrate by feeding your probiotics with resistant starch (green bananas or plantains, beans, peas, lentils, and potatoes or rice that have been cooked and cooled) (R) or taking a supplement (R).
Conclusion: The Significance of BDNF
The level of BDNF in our bodies, influenced by both genetics and lifestyle choices, plays a critical role in our brain health, cognitive function, and overall mental well-being. Even if you carry the 'Met' variant of the BDNF gene, there are still numerous ways to positively influence your BDNF levels. By incorporating the ten strategies discussed above, you can improve your brain's health, cognitive function, and mental resilience. After all, while we may not have control over our genes, we do have control over our habits and lifestyle choices.
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