What You Need To Know About BDNF
Researchers now recognize that the brain continues to reorganize itself by forming new neural connections throughout life.
Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF is one of the most active .
In the brain, BDNF is active in the hippocampus, cortex, and forebrain – areas vital to learning, memory, and higher thinking. Hence, BDNF is important for long-term memory .
It is also expressed in the retina, motor neurons, the kidneys, saliva, and the prostate .
BDNF has been shown to play a role in neuroplasticity, which allows nerve cells in the brain to compensate for the injury, new situations or changes in the environment .
BDNF helps to support the survival of existing neurons and encourages the growth, regeneration, and creation of new neurons and synapses .
It’s important to realize that BDNF levels can be different in different places. So you have blood BDNF levels, CSF BDNF levels and BDNF levels in various brain locations. In healthy people, there’s actually no correlation between BDNF in the blood and CSF .
However, a different study says that BDNF in the blood is thought to be a reliable and sensitive marker of its variations occurring in the brain (Lommatzsch et al. 2005) .
Since BDNF can cross the brain barrier, it would make sense .
Blood BDNF decreases significantly with age .
BDNF and Your Health
BDNF also can help you lose weight.
BDNF suppresses food intake through hippocampal signaling .
BDNF infusion into the rat brain has been shown to lower body weight and to suppress appetite .
BDNF increases energy metabolism in obese diabetic animals, partly through activating the stress response and inducing UCP1 – an uncoupling protein that creates brown fat, which is easily burned for fuel .
In healthy humans, the fatter people are the lower their blood BDNF .
Lower BDNF could be a cause, a side effect of being overweight or related to a factor that decreases both weight and increases BDNF – sleeping more, eating less, etc… But it definitely seems like more BDNF is causing people to weigh less.
BDNF triggers slow wave sleep by promoting “synaptic potentiation” .
In mice, the level of exploratory behavior induces BDNF  – in humans, this would equate to mental and physical stimulation or novelty. BDNF, in turn, is the signaling molecule that causes an increase in slow wave sleep [11, 12].
So the more stimulated or sleep-deprived you are, the more you need slow wave sleep, and the molecular link is BDNF.
When BDNF levels are high, acquiring new knowledge is easier, memories are retained, and people feel happier.
Studies have shown that brain size is correlated with lifespan and BDNF may be that link, since it increases insulin sensitivity .
BDNF causes blood pressure to increase, which is perhaps the most significant risk factor for heart disease.
When BDNF is injected in the rostral ventrolateral medulla (mice), blood pressure increases .
BDNF overexpression in the paraventricular nucleus (rats) increases blood pressure via angiotensin type-1 receptor-mediated mechanisms.
Increased BDNF in forebrain may cause difficulty in learning and poor memory formation .
Indeed, people who are genetically lower BDNF producers have lower systolic blood pressure .
The Circadian Rhythm
When light hits your retina, it gets transmitted to your hypothalamus and in the particular suprachiasmatic nucleus (SCN). This causes the SCN neurons to fire, via the neurotransmitter glutamate.
The SCN is the central clock and is the conductor of your circadian rhythm.
When the SCN fires, that’s when the circadian rhythm starts and you wake up.
BDNF can enhance glutamate neurotransmission in SCN neurons and potentiates glutamate-induced shifts of the circadian rhythm .
BDNF secreted at night is probably required for light-induced shifts in the circadian rhythm .
In mice, BDNF injection at 4 PM caused the circadian rhythm to be pushed off by 2.3 hours (so if you wake up at 8 AM, you’d wake up at ~ 10 AM)… BDNF treatment during 10 PM caused the circadian rhythm to be pushed back 2.3 hours (so if you wake up at 8 AM, you’d wake up at ~ 6 AM). No phase shift occurred when BDNF was applied during the day at 7 AM.
BDNF-induced circadian shifts were dependent on Glutamate/NMDA receptor stimulation of the SCN .
So it’s quite plausible to say that if you’ve got low BDNF, it could be harder to set your circadian rhythm.
On the other hand, if you’re a high BDNF producer, your SCN may over-fire and burn out more quickly.
If you’re getting the sun, that increases BDNF and so you’re covered if you get adequate sun.
Socializing and Love
BDNF blood levels were correlated with romantic attachment, but only in women. The higher the BDNF, the lower women scored on an avoidance test (ie, they were more friendly and likely to form bonds) .
So BDNF may play a role in promoting social relationships through a specific decrease of avoidance and fear of the stranger and unfamiliar individuals .
Estrogens induce BDNF synthesis in several brain regions .
Are You a High or Low BDNF Producer?
If you’ve got your 23andme or another genetic testing, you can find out if you’re a high BDNF producer.
Here is my version of BDNF SNPs:
- RS11030101 (BDNF) AT
- RS11030104 (BDNF) AA
- RS12273363 (BDNF) TT
- RS12273539 (BDNF) CC
- RS2049046 (BDNF) AA
- RS56164415 (BDNF) GG
- RS6265 (BDNF) CT
- RS7103411 (BDNF) TT
- RS8192466 (BDNF) GG
How to Increase BDNF
If you’re a high BDNF producer (more to come) or you have an overactive stress response, you want to select wisely as to which supplements you include.
People suffering from insomnia had lower BDNF levels compared with sleep-healthy controls. This is one method by which stress decreases BDNF – by ruining sleep. It’s thought that whether stress causes mental disorders depends on if sleep is maintained or disturbed .
In anti-depressant therapy, elevated BDNF is a predictor that antidepressants are working. However, BDNF doesn’t actually coincide with a decrease in depression, and for this reason, it’s thought that much of predictive effect is based on sleep. This means that BDNF is a marker of how well you’re sleeping and good sleep is what’s needed for an anti-depressant effect .
Getting good sleep is one of the most important things you can do for your health. I rarely use alarm clocks. Don’t try to get less of this to accomplish more.
Acute stress more significantly decreases BDNF .
People who are under a lot of stress show less BDNF .
Sun is something that I’ve been a proponent of for a long time.
In an analysis of 2,851 individuals in the Netherlands, it was found that blood BDNF increased in the spring and summer and decreased in the fall and winter. BDNF levels correlated to the number of hours a person was exposed to the sunshine .
Supplemental vitamin D in postmenopausal women actually decreases BDNF .
Sun is beneficial by having high energy photons/Blue light, infrared, UVB, and UVA, all four of which have unique and important properties for the body. I’m willing to bet there’s more to it, but I just don’t know what yet.
In sedentary male college students, high-intensity exercise boosted both the BDNF levels and memories .
The changes in BDNF levels were found in nerve cells within days after exercise in both male and female rats and were sustained even several weeks after exercise .
In rats, low intensity is actually better than the high intensity at increasing BDNF .
This accords with evidence in normal rats that show low-intensity exercise can improve synaptic plasticity better than high-intensity exercise .
This is why I like to take walks as a staple of my exercise regimen. I find it clears the mind.
Cold and Heat (Sauna)
I have an Infrared Sauna and then take a cold shower. I also expose myself to cold often. I also have many cold devices such as an Ice Helmet/Cryohelmet and even an ice vest.
Calorie restriction increases BDNF in rodents, but not in humans in this study 
A highly stimulating early social environment in animals increases BDNF .
In mice, the level of exploratory behavior induces BDNF  – in humans, this would equate to mental and physical stimulation or novelty.
When you learn things or challenge your brain, the brain increases BDNF because of its important role in memory .
I used to do N-Back many years ago, but I found the best stimulation to be the LSAT.
I don’t practice it anymore because I don’t have the time and because I don’t need it.
These games could be useful if you aren’t getting in a flow state in the day. I don’t advocate them if you are getting in the flow.
You know you’re in flow if:
- You’re consumed with a task
- You’re not thinking about the future or the past
- You’re not questioning if you like what you’re doing
- You’re not bored
- You’re not stressed
I previously discussed the importance of getting enough sleep, so this may seem odd. The difference is that this is not chronic sleep deprivation.
Sleep deprivation means staying up all night and this can be used to jumpstart BDNF.
In one study, they use it for this purpose with the anti-depressant Sertraline (Zoloft).
The first single sleep deprivation and a series of three subsequent sleep deprivations accelerated the treatment response that significantly decreased depression and increased BDNF levels .
Steve Jobs used to practice this. I don’t like it.
It kills my motivation for a couple of days and worsens my mood when I pull all-nighters.
Keep to a Circadian Rhythm
It’s plausible and I’d say likely that when your circadian rhythm is dysregulated, BDNF is decreased. We see this in people with traumatic brain injuries, who have a dysregulated circadian rhythm and lower BDNF production  – even though you’d expect BDNF to go up to heal the brain injury.
I can’t find more studies on this, but I’m willing to wager that circadian dysregulation will negatively impact BDNF.
- Ketogenic Diet 
- Stay away from the SAD diet – stay away from a high sugar and high saturated fat diet i.e. SAD diet… 
- Fish oil/DHA [53, 54]
- Hi-maize/Resistant starch – converts to butyrate, which causes an increase in BDNF 
- Honey: FOS, GOS (Prebiotics) …
- Blueberries 
- Cocoa (flavonoids) 
- Soy – Both estradiol and soy phytoestrogens significantly increased BDNF in the frontal cortex of female rats .
- High salt intake 
Liquid Diet – Chew!
A liquid diet in mice actually results in higher BDNF in the hippocampus, but lower levels of another ‘downstream’ protein that BDNF is supposed to increase.
Think of BDNF as being the first domino, but for some reason later down the line, there’s less of another domino. If you’re missing a domino at the end, it doesn’t matter how much of the first domino you have, because it’s the later domino (TrKB) that controls your genes.
The findings suggest that reduced chewing induced by a liquid diet in early childhood may impair memory and the learning ability, accompanied by a neuronal loss in the hippocampus .
This is why if I have mostly a liquid diet, I make sure to chew Gum.
I use all of the linked devices.
- Butyrate 
- Quercetin  and kaempferol
- Caffeine 
- Curcumin produces neuroprotective effects via activating BDNF/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons .
- Niacin 
- Magnesium  (in prefrontal cortex, hippocampus)
- Lactate – Researchers injected people with lactate and found BDNF levels rose after .
- Magnesium L-Threonate – Elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, the density of presynaptic puncta, and synaptic plasticity in the prefrontal cortex .
- Inosine 
- L plantarum 
- Gynostemma 
- EGCG 
- Lithium – Elevates BDNF by inhibition of GSK-3, which also increases skeletal muscle growth .
- Olive leaf
- NAC 
- Theanine  – Increases BDNF and attenuates cortisol-to-DHEA, also has low affinity for AMPA, kainate, and NMDA receptors . (unrelated, but did you know it’s an NMDA agonist?)
- Rhodiola/Salidroside 
- Resveratrol 
- Rehmannia 
- Ginseng – When pretreated orally, GRb1 significantly inhibited the stress-mediated decline of BDNF level whereas it further increased the stress-mediated elevation of HSP70 level .
- Baicalin 
- Bacopa – In rats, bacopa increased BDNF when the animals were exposed to chronic unpredictable stress .
- Fo-ti (He-Shou-wu) 
I am not recommending the usage of these, just listing them for informational purposes. Some of them can be beneficial if used in the right way.
- Semax (ACTH analog) 
- Citalopram (Celexa, SSRI) 
- Tianeptine (Tricyclic) [95, 96]
- LSD 
- Ketamine 
- Cocaine  – not necessarily good because it increases in the reward regions (mesolimbic pathway), which probably causes addiction…complex… I don’t recommend anyone take cocaine.
- MDMA  – increases in some areas, decreases in others… Increases in response to damage…
- Ladostigil (experimental drug) – A reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor. Enhances expression of GDNF and BDNF .
- Rasagiline 
Cerebrolysin actually doesn’t increase BDNF in mice bred for Alzheimer’s , but for some reason, I thought it did. That’s why it’s good when I make sure to back up what I say with sources.
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