Brain-Derived Neurotrophic Factor (BDNF): The Nootropic That Lasts A Lifetime

Jay Campbell

By Jay Campbell

March 17th, 2022

 

Cognitive enhancement is all the rage in the 21st century.

We live in the Information Age, where knowledge is the key to power and wealth… so why would you NOT want to maximize your ability to take it all in?

One newly discovered hack to achieve this goal is maximizing the production of a naturally-occurring protein in your brain.

A protein called “BDNF” (a.k.a. brain-derived neurotrophic factor) that:

  • Effortlessly gets you into the desired “flow state” sought after by the world’s most influential artists
  • Helps you memorize vast volumes of complex information no matter your age
  • Sharpens your focus like a razor by 10-fold

This article is going to tell you about BDNF’s wonderful life-changing effects and how to enhance your brain’s BDNF production for extreme productivity.

So if you want to optimize your brain for peak mental performance, keep reading!

What Is BDNF?

BDNF is what’s known as a neurotrophin: A “growth factor expressed in the brain and peripheral tissues, which regulates many aspects of neuronal function, including proliferation of neural progenitors, neuronal morphology, synaptic plasticity, and even cell death following injury.”

Its discovery in 1982 was predated by the finding of NGF (Nerve growth factor), a protein responsible for the growth and survival of select neurons (i.e. brain cells):

“Brain-derived neurotrophic factor (BDNF) was first isolated in the 1980s, nearly three decades after the identification of the related factor, nerve growth factor (NGF).

NGF, identified by Rita Levi-Montalcini, Victor Hamberger, and Stanley Cohen was recognized to support the survival of subpopulations of peripheral neurons, prompting Yves-Alain Barde and Hans Thoenen to search for a growth factor that exhibited similar properties for other populations of neurons.

BDNF was initially purified from pig brain, and was found to be expressed at low concentrations”

BDNF appears to exist in two forms within the human body — a “pre-mature” form and a “mature” form:

“[BDNF] is synthesized in a pre-pro form consisting of 247 amino acids. Pro-BDNF is packaged into secretory vesicles and is then released from the neuron through either constitutive secretion or activity-dependent release.

…After its release from the neuron, the pro-domain of pro-BDNF is proteolytically cleaved by plasmin or metalloproteinases, giving rise to mature BDNF. Recent findings suggest that the mature form of BDNF is predominant and of greatest physiological relevance in the adult CNS [central nervous system].

BDNF protein is widely distributed throughout the adult brain in almost all cortical areas, as well as several subcortical and spinal cord regions. BDNF binds to two receptors of distinct classes: tropomyosin-related kinase receptor type B (TRKB), which is a tyrosine kinase receptor of the tropomyosin-related kinase (TRK) family, and the p75 receptor, which is a member of the tumour necrosis factor (TNF) receptor family.

TRKB is the key receptor for BDNF in the adult brain, owing to its wide pattern of expression and a higher binding affinity for BDNF than p75.”

Or as another Nature paper so eloquently put it, there seems to be a cycle between neuron behavior and BDNF production:

“Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors.”

Ok, so we have something responsible for neuronal health… but why does that matter to us?

Why Is BDNF Important?

A lot of this section is paraphrased from Chapter 11 of The Metabolic Blowtorch Diet, so I’ll be brief.

BDNF is responsible for four main functions:

  • Allowing for new connections between neurons in the brain to form
  • Strengthening the connections between existing neurons
  • Activating the creation of new neurons via neurogenesis. 
  • Preventing apoptosis (cell death) to help neurons survive

As I mentioned in The TOT Bible, this regenerative process is an essential part of healing in PTSD-stricken veterans:

“Russ Scala states that one of the keys to the healing process for Veterans is the development of new brain tissue and brain cells, particularly in the hippocampus (via neurogenesis). And central to neurogenesis is Brain-Derived Neutrophic Factor (BDNF), a protein that triggers the process. BDNF promotes improved mood via antidepressant activity and lowers cortisol levels, two crucial outcomes that Veterans desperately need.”

Collectively, these four processes aid in a cognition-enhancing process known as “neuroplasticity”:

“Twenty years ago, the prevalent view in psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life.

In the past 20 years, another view has supplanted this one, showing that although the juvenile period is especially suited to neuroplastic adaptation, there is hard neuroplastic change later in life as well.

…At base, “neuroplasticity” simply refers to the malleability of the brain, observable as changes in neuronal structure and connectivity, typically as a consequence of influences outside of the brain.”

And it’s critical to point out neuroplasticity doesn’t just happen by sitting around and waiting:

“Neuroplasticity is activity-dependent because sensory activity is the means through which the outside world influences the brain. Repeated motor or cognitive activity can also drive neuroplastic changes.

Regardless of the source, a sustained change in a pattern of neural activity is a necessary trigger for neuroplasticity. The change in neural activity pattern leads to a reorganization in neural circuits, which produces long lasting functional change”

This is the “mental sharpness” you see in young bright people and older individuals who seem to get smarter with each passing year.

In effect, the combined firing and wiring of new neural connections slowly changes your brain structure (as witnessed in the brain healing itself after damage from a neurological disease/injury).

And in turn, you have the ability to form and retain new memories, skills, and thoughts… all thanks to BDNF.

But this process of neuroplasticity – though it is a lifelong process – requires enough BDNF production in the first place.

Once your BDNF production is fully optimized, the brain health benefits are numerous in size and scope:

Increased cognitive function, mental clarity, improved long-term memory, rapid learning comprehension… sounds like the perfect all-in-one nootropic pill!

But here’s another BDNF health benefit “science” has yet to catch up to: Its ability to act as a divine gateway to the portals of higher consciousness.

In Living A Fully Optimized Life, I talk about the link between BDNF and connection to the “source energy”(also known as scalar life force energy) of the universe:

“It allows you to become fully aligned with “WHAT IS” while elevating your consciousness to higher levels. In life, so many things are hidden in plain sight.

Elevated consciousness enables you to pick up on life’s subtleties and perceive things you were once oblivious to. Think of it as the difference between “believing” and KNOWING.

As a free-willed human being, your goal SHOULD BE to increase your consciousness and BDNF puts you on the fast track. It is hard to truly describe this experience if you’ve never fasted for extended periods of time.”

Don’t forget this works the opposite way… if BDNF production is sub-optimal, you have a higher chance of contracting the following diseases:

I could go on and on, but the evidence strongly points in one direction:

Increasing BDNF production is critical for faster and efficient neuron repair, and by extension a direct path to better brain health.

Top 9 Ways To Naturally Maximize BDNF Production

So what can we do to improve BDNF production in our brains?

Before I get into my best time-tested strategies, there are two important things to remember…

First, your body’s BDNF levels naturally decline with age.

Second, and most importantly, BDNF levels can be naturally increased at any age through the right interventions.

This means your mental health is 100% in your control.

A healthy, high-performance brain is well within your grasp if you consistently do the following things over time…

Practicing Intermittent Fasting On A Frequent Basis

Intermittent fasting can be summed up in one sentence: You don’t eat for an extended period of time and then consume your daily caloric intake within a shorter period of time (ex. skipping breakfast while eating lunch and dinner).

This practice of dieting has been shown to increase BDNF levels in several studies:

(For more information on the mechanism of how and why BDNF increases upon intermittent fasting, read this article)

My recommended intermittent fasting protocol is The Metabolic Blowtorch Diet: It will dramatically enhance BDNF production during the long fasting windows, providing you with all-day energy and maximum focus. 

If you go down this path, I have a few insider tips to share with you:

  • BDNF is a protein released in the brain after roughly 17-22 hours of fasting, and research shows it spikes again during prolonged fasting (after 43-44 hours).
  • Max out your fasting windows — If you have 24 hours in a day, you would have an 18-21 hour fast window and a 3-6 hour feeding window. 
  • 2-3 of these fasts a week will turn your body into a BDNF-producing machine. 

But for those of you who want the most extreme form of fasting for fat loss and even more BDNF, check out Guaranteed Shredded.

Doing Frequent High-Intensity (Aerobic) Exercise

Nobody will ever debate against high-intensity exercise and its positive effects on regulating your mood, while also improving your memory.

The same goes for BDNF, and there are multiple studies in humans showing the well-established connection between more exercise and increased BDNF production.

Here’s the really cool thing: Post-exercise increases in BDNF have been observed in adolescents and young adults, regardless of training level

In a 2015 meta-analysis of 29 studies examining over 1,000 subjects, BDNF production was boosted after one session of exercise AND after a regular program of exercise

(NOTE: One study found resting BDNF levels were lowered in trained middle-aged individuals)

A separate meta-analysis in 2017 of 55 studies found the same thing, noting a greater BDNF effect in males than in females.

Moreover, BDNF goes up after both strength and endurance workout sessions (although one study found aerobic exercise led to larger resting BDNF concentrations than strength training).

One cool rat study even found regularly exercising can decrease the impairments induced by sleep deprivation through the mechanism of BDNF production!

These findings suggest that regular exercise can exert a protective effect against hippocampus-related functions and impairments induced by sleep deprivation probably by inducing BDNF expression.

And while this is up for debate, the largest increases in BDNF seem to happen when training sessions are longer and more intense. (while also being negatively correlated with time spent sedentary).

Even with the amazing consistency seen in the scientific literature, let’s get one thing clear: You MUST exercise consistently if you want to experience a significant change in BDNF levels and increase blood flow to the brain.

Additionally, please do not make the mistake of getting too caught up in the “right” form of exercise.

My personal recommendation for exercise that best increases BDNF — specifically cardio — is the following:

low-impact endurance training 2-7x per week (30-45 minutes per session) at a low to moderate intensity (65-80% of maximum heart rate, so ~125-140 BPM) depending on your body fat levels.”

Fasted cardio in the morning will do wonders to jack up your BDNF levels and give you a rush of feel-good chemicals that will brighten up your mood, and the spike in BDNF will return to a normal level after several minutes (or even a few hours).

Other people will disagree, claiming interval training leads to greater increases in BDNF than continuous, steady-state training.

Don’t get caught up in the debate… just get on the bike and pedal!

My long-time friend Daniel Kelly has personally experienced post-exercise BDNF himself, and talks about it in this old podcast:

 

Eating A Clean, Healthy Diet

Any doofus with two brain cells can put 2 and 2 together — a crappy diet is terrible for brain health:

“In Western society, the prevalence of a hyper-caloric diet consisting of a high sugar intake and highly processed foods coincided with an exponential rise in diabetes and metabolic syndrome as well as cardiovascular diseases and cancer. Evidence emphasizing the unfavorable effects of ‘irresponsible eating’ is emerging in regards to the big three Western diseases … cardiovascular disease, diabetes and cancer.”

But what about BDNF specifically?

Two rat studies (here and here) showed a clear reduction in BDNF levels within the brain when they were fed a diet containing high amounts of saturated fats and simple refined sugars.

Same goes for excessive consumption of fructose, except this study found negative effects on the gene responsible for encoding the BDNF protein.

So whenever you feel like shit after binging on McDonald’s, now you know why.

This leads us to the foods and practices you SHOULD follow if you’re serious about keeping BDNF production as high as possible and your risk of cognitive decline as low as possible.

The same rule your grandma has been telling you for ages: If it didn’t grow from the ground, probably not a good idea to eat it!

Getting Your 8 Hours Of Sleep Every Night

Likewise, failing to give your body the rest it deserves is also a guaranteed way to lower your BDNF levels.

After all, it plays an integral part in regulating your sleep cycles:

“EEG slow waves are the hallmark of deep NREM [non-rapid eye movement] sleep and may reflect the restorative functions of sleep. Evidence suggests that increased sleep slow waves after sleep deprivation reflect plastic synaptic processes, and that brain-derived neurotrophic factor (BDNF) is causally involved in their homeostatic regulation”

…BDNF contributes to the regulation of sleep slow wave oscillations, suggesting that genetically determined variation in neuronal plasticity modulates NREM sleep intensity in humans.”

(For more intel on the importance of proper sleep, read this article)

Not only is BDNF negatively associated with symptoms of insomnia, but its production also goes down with continued days of restricted sleep.

Moreover, in 2013 scientists discovered a key connection between BDNF, stress levels, and sleep:

“We found a significant interaction between stress and insomnia with an impact on serum BDNF levels. Moreover, insomnia severity groups and score on the PSS [Perceived Stress Scale] each revealed a significant main effect on serum BDNF levels. Insomnia severity was associated with increased stress experience affecting serum BDNF levels.

Of note, the association between stress and BDNF was only observed in subjects without insomnia. Using a mediation model, sleep was revealed as a mediator of the association between stress experience and serum BDNF levels.”

This relationship is still being examined, but the connection shouldn’t be surprising to anybody with common sense:

“A low neurotrophic activity is associated with a reduced number of cells in the prefrontal cortex, amygdala, and decreased hippocampal size, indicating that BDNF may play an important role in the development of depression… Antidepressants that decrease BDNF levels can be effective in treatment of depression, however can alter sleep pattern.”

“Sleep impairment may lead to severe physical and mental problems, as sleep deprivation is usually followed by enhanced vulnerability to stress which can decrease BDNF production. It’s known that serum BDNF levels are associated to sleep, even in patients who do not have sleep problems”

Want to improve your body’s BDNF-producing ability?

Get enough deep sleep every night without fail.

One final note — make sure your lights are turned completely off if you want your BDNF levels high while you sleep.

Exposing Yourself To Bright, Natural Sunlight Every Day

However, the daytime is when you want to be sitting in the sun for your best chance at keeping BDNF levels high during the day.

The first evidence for this came in 1992 from a rat study:

“Keeping adult rats in the dark or preventing normal activity of retinal ganglion cells by intraocular injection of tetrodotoxin significantly decreased the levels of BDNF mRNA in the visual cortex but not in other cortical areas. Exposure to light after a period in darkness rapidly restored the mRNA to control level.

…the levels of BDNF mRNA are rapidly regulated by sensory input during development and in adulthood. BDNF may therefore play an important role in formation and in activity-dependent modulation of specific connections in the visual cortex.”

Then, in 2012, a Danish study examining BDNF levels in 2,851 patients recruited for a prior study on depression and anxiety found something interesting:

“Analyses by month of sampling (monthly n’s >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ß) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ß = −0.17, P<.0001).

…We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations and this could partly explain the observed monthly variation.

These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression.”

Its good news for people suffering from depression during the dark winter months… especially since one rat study published a year later found that bright light exposure therapy promoted neurogenesis via increased BDNF production.

Sadly, a double-blinded placebo-controlled trial found that Vitamin D supplementation of 2,000 IU per day for 10 weeks had no effect on BDNF levels in older adults (>60 years old).

My first guess is that they used too low of a dose for Vitamin D (I would have recommended 5,000 IU at the lowest), but it could be the case that sunlight beats out artificial supplementation.

Keeping Your Stress Levels Low And Stable

Expanding on my earlier recommendation for deep sleep, there is certainly a much stronger link between BDNF and stress.

Numerous rat studies (here, here, here) consistently show reduced BDNF expression when they are acutely or chronically stressed out.

And luckily enough, this same observation was noted in a double-blind randomized controlled trial of middle-aged adults:

“Forty-eight men and women between the ages of 38 and 62 reporting high-demanding work activity but with an overall positive attitude towards their personal life were recruited. Subjects were divided in two group (24 patients each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo. 

…Results showed that, as compared to healthy, non-stressed individuals, stressed ones has a trend decrease of BDNF and this was significantly increased by LD 12-1227 supplementation and the same inverse phenomenon occurred to salivary amylase”

At the start of this article, I noted how BDNF was a gateway to raising your vibration.

One way to get there is through the practice of meditation… although the literature is mixed on this method of increasing BDNF.

In a pilot study consistently of thirty 2nd-year medical students (18-20 years old), a four-day mindfulness meditation program found that BDNF levels decreased (although it was not statistically significant).

Yet another pilot study found the opposite result when a similar program lasted 90 days:

“Thirty-eight individuals (mean age: 34.8 years old) participating in a 3-month yoga and meditation retreat were assessed before and after the intervention for psychometric measures, brain derived neurotrophic factor (BDNF), circadian salivary cortisol levels, and pro- and anti-inflammatory cytokines.

…As hypothesized, increases in the plasma levels of BDNF and increases in the magnitude of the cortisol awakening response (CAR) were also observed. The normalized change in BDNF levels was inversely correlated with BSI-18 anxiety scores at both the pre-retreat (r = 0.40, p < 0.05) and post-retreat (r = 0.52, p < 0.005) such that those with greater anxiety scores tended to exhibit smaller pre- to post-retreat increases in plasma BDNF levels.

…The increased BDNF levels observed is a potential mediator between meditative practices and brain health”

This makes sense when you consider that all spiritual practices take time and dedication in order for fruitful results to appear.

There’s no other literature on these types of methods and their effects on BDNF levels, although one small rat study suggests music can positively influence BDNF production.

So keep your stress levels low, and remember: The gift is in the shit ie we evolve and grow through contrast!

Maintaining An Active Social Life

There’s no fun in being the “lone wolf”, or in being an outcast who misses out on human bonding and interaction… the still-ongoing pandemic has made this exceedingly clear.

A rat study published in 2006 found that “early social enrichment” for young rat babies not only affected their behavior later in life, but also their BDNF levels:

“The CN [communal nest] consisted of a single nest where three mothers kept their pups together and shared care-giving behavior from birth to weaning (postnatal day 25).

Compared to standard laboratory conditions, in CN condition, mouse mothers displayed higher levels of maternal care. At adulthood, CN mice displayed higher propensity to interact socially and achieved more promptly the behavioral profile of either dominant or subordinate male. Furthermore, CN adult mice showed higher NGF levels, which were further affected by social status, and higher BDNF levels in the brain.”

The same team of scientists published another study within the same year, noting how the behavior induced later in life consisted of greater levels of anxiety and depression.

Even if you discount how changes in behavior and brain function can be induced by bad early experiences, something such as isolation following an injury can also lower BDNF production:

“…we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice.

Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety.”

A good reason to avoid staying in a hospital bed unless your life absolutely depends on it (and I’m not just talking about the ludicrous bills you have to pay when you leave!)

Even in a small human study that had its fair share of limitations, women with higher BDNF levels tended to be more friendly towards strangers:

“The results of the present study showed that BDNF plasma levels and romantic attachment, assessed by the ECR, are related, but differently in the two sexes. In fact, women showed a significant and negative correlation between BDNF levels and the ECR [Experience in Close Relationships] avoidance scale, i.e. the higher the NT [neurotrophin] concentration, the lower the avoidance score.

This suggests that BDNF may play a role in promoting social relationships through a specific decrease of avoidance and fear of the stranger and unfamiliar individuals: this is consistent with the recently proposed involvement of BDNF in reducing social stress responses, as shown by the association between BDNF Val66Met polymorphism and vulnerability to social stress”

The human mind thrives on the stimulation provided by social connection and bonding, so why be a shut-in for no reason?

Using Golden Age Peptides & Compounds For Increasing BDNF

There’s only so much we can do with natural lifestyle interventions before we need some extra help.

Fortunately, I’ve written extensively about several therapeutic peptides that are proven to up-regulate BDNF production:

The best part about all these peptides is Limitless Life Nootropics has them in stock at >99% purity.

No other vendor provides their level of exceptional customer support and product quality control.

Use code JAY15 to get 15% off your order! 

There are also select compounds which have been studied with respect to improving BDNF levels:

You don’t have to chronically use all of these compounds at the same time… pick one and see what works best for you.

Actively Stimulating and Engaging Your Mind

Remember when I said fully optimizing your BDNF levels will require a conscious effort on your part?

Exercise alone will not be sufficient for cognitive optimization – you must pair the physical stimulation with some mental stimulation immediately after.

Once you are rigorously applying all of the other strategies I’ve talked about, it’s time to put your cognitive gains to work… because there’s no point in a BDNF-friendly lifestyle if you don’t apply it to your life.

As supplement expert Shawn Wells told me on my podcast:

“Our routines are making us smarter and dumber at the same time. How can we challenge our brains to stay sharp and focused? How do you stimulate BDNF?

…BDNF doesn’t just protect existing neurons and improve the functioning of nerve signaling, it stimulates and creates new ones. We get more BDNF by challenging our brains to learn new things and working on maintaining our fluid intelligence”

What does this mean?

It means you need to spend as much time as possible on the difficult tasks that require brainpower.

Producing content, tapping into your creative energy, thinking critically about complicated topics, writing down your thoughts… these things require zero distractions and an optimal state of mind.

It’s the “use it or lose it” principle in action, something observed specifically in mice studies and human studies with respect to BDNF production.

You get the gears going with something challenging, lock yourself into the flow state, and let the magic happen:

“Challenging your brain with new tasks or skills will increase BDNF production because of BDNF’s role in memory and learning.  It can be as simple as playing brain games, like those found in Brain HQ, or learning a new skill (cooking, knitting, playing an instrument, learning a language).   Doing anything that is different or challenging can qualify as mental stimulation.”

I’ll end this section with a tip taken right out of Guaranteed Shredded:

  Schedule your most brain-intensive work between your 16-22 hours of fasting because that’s when BDNF will be the highest.

Ideally, your work is done right after fasted cardio and you have a cup of black coffee (no milk or sugar) by your side!

Additional Reading Resources For Obtaining Fully Optimized BDNF Levels

If you’ve already read my article on improving mitochondrial health, you may notice the same pieces of advice repeated here.

DUH! The design of the human body was not a mere accident — everything is interconnected in one way or another.

It shouldn’t be a shock to see the trifecta of “eat clean, train hard, sleep well” improve multiple biological systems in many different ways, and BDNF is no exception.

You need to combine several strategies at once for a massive short-term and sustained long-term boost in BDNF levels.

But now you know the game-changing benefits of BDNF production, and I just gave you the step-by-step formula for extraordinary levels of peak cognitive performance.

Before you go, allow me to share some additional intel that will help you on your journey…

These two books on Amazon — here and here — are deep academic investigations into the wonders of BDNF for the clinical nerds out there.

MyBioHack has compiled +140 ways to naturally increased BDNF production, some of which are not featured in my article. 

SelfDecode dives deep into genetics and how your genotype determines your ability to benefit from BDNF

As always…

Raise Your Vibration To Optimize Your Love Creation!

PS – For more highly advanced BDNF-boosting hacks and cognitive-enhancing tactics that only my private coaching clients know about, join The Fully Optimized Health Private Membership Group.

It’s your greatest opportunity to fully optimize your health, gain total access to myself and network with high-level men and women looking to 10X their life.

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