Procrastination may feel like laziness but it’s actually a self-defense mechanism that can be explained through neuroscience. How our brains are wired has a lot to do with why we procrastinate.
The Neuroscience of Procrastination
Two brain regions, the limbic system and the prefrontal cortex, play an important role in procrastination. The limbic system is your brain’s oldest and most dominant part. It is involved in actions that have to do with survival, such as:
Feeding our children
Fight-or-flight responses
Reproduction
Whereas, our prefrontal cortex is newer and less developed. It is involved in complex actions like decision-making, reasoning, and impulse control.
Oftentimes when we procrastinate our limbic system is winning over our prefrontal cortex. After all, our limbic system is much older and stronger than our prefrontal cortex.
Another reason we procrastinate is because of how our brains have been wired over the years. Voluntarily delaying a task leads to instant gratification and a release of dopamine, the hormone that makes us happy. Over time our brains begin to associate delaying tasks with a dopamine release. We procrastinate because it gives us happiness in the moment instead of achieving a big dopamine rush once we complete the task.
We also procrastinate for the rush of adrenaline we get from having to complete a task at the last minute. The stress of an impending deadline brings about a release of adrenaline and makes us excited.
How to Stop Procrastinating
Fortunately, eliminating procrastination is within your control. A few tweaks here and there in our daily routine can reduce the likelihood of putting things off.
Break impossible projects down into small baby steps
The thought of tackling a big project itself is daunting. Breaking down projects into smaller action items makes us more likely to actually do them. Once your task has been broken down, start off by taking on the most dreaded action item first. It’s much easier to complete a bigger task when it’s broken down into smaller chunks.
Delegating small tasks to others, or asking for help can also reduce procrastinating behavior because there are now more shoulders to carry our burden.
Take on the task for 10 minutes only
If you’re putting off something like organizing your kitchen or working on homework, tell yourself you’ll do it for only 10 minutes. Set a timer on your phone and then begin your task. Oftentimes you will get really involved and feel the momentum by the 10-minute mark and will continue working even after the time is up.
Even the most daunting of tasks can be completed if we just convince ourselves we’re only doing it for 10 minutes.
Re-frame the actions and little steps as wins
Reframing the action makes us more likely to tackle the task instead of delaying it. Instead of thinking about how you have to work for four hours straight to get a project done, reframe your thinking. You could say, “Once I finish this project in four hours, I get to enjoy the rest of my day.”
You could reframe the task as a challenge as well. Instead of thinking about how difficult and tedious the project is, take it as a challenge. Think “I wonder if I can complete this task in half the time and with better results than I’m anticipating.”
When we feel like we have to do something, we are externally motivated. It’s hard to start taking action right away when we’re relying on external motivation. Reframing your task allows you to channel internal motivation.
As you check things off your to-do list, celebrate all you’ve done. It will get you more motivated to continue.
Find the right environment to work in
Distractions can really hamper progress. Ensuring that you’re in a distraction-free work area helps you stay on task. If you’re working on the computer, close off other tabs, and turn your phone to “do not disturb”. Even minor distractions make us lose focus.
Avoid multitasking as well, Our brains can only focus on one task at a time. The more distracted you are by other tasks, the less efficient you will be.
Being in a calm environment can boost productivity. Being in a room that is well-lit, has a comfortable temperature, and is quiet can allow you to stay focused and get more done. Having greenery around you can also boost productivity.
Take breaks
Research has shown that taking breaks in between tasks allows us to be more productive than if we attempt to work away for hours at the end. This is because when we take a break, our brain revisits the work we were doing. If we were struggling with some aspect of it, our brain reviews it during a break. When we return to work, we’re more refreshed than before.
Use little dopamine boosts (e.g. exercise, sun)
The reason we procrastinate is that we get a dopamine boost from doing so. An alternative to tackling this problem is to take on the task and conclude with an activity that gives a dopamine boost. For example, you can reward yourself with a healthy snack, go for a walk, or sit in the sun after the work is finished.
Including actions that naturally release dopamine will give you pleasure and satisfaction in getting the task done instead of putting it off.
Have others hold you accountable
We’re more likely to complete a task if we have pressure from others like family or friends. Sometimes people will let their friends know they’re going on a diet so their friends can hold them accountable when they’re about to falter. Similarly, letting others know you’re about to do something will force you to take action due to positive pressure from others.
Heal past traumas
If you find yourself in a cycle of procrastination where you just can’t get yourself to do something important like eat healthily or go to sleep on time, it could be a form of self-sabotage. Self-sabotage can result from childhood trauma that is unhealed and is rearing its head by preventing you from achieving your goals and living a better life.
Past trauma can become the mental dialogue that prevents us from doing something that we know will bring a positive change in our life. It’s best to address your traumas so you can rid yourself of the trauma that’s holding you back and causing cyclical procrastination. It’s difficult to deal with and resolve trauma on your own.
Use nootropics that boost brain energy and dopamine
Nootropics like Dopa Drops and Apex can help us with the motivation and focus we need to take action and not procrastinate.
Dopa Drops increase vitamin B levels and dopamine precursors in the body allowing the body to be more sensitive to the dopamine already present. It also allows the body to release dopamine over a longer period. An increase in dopamine keeps us energized and motivated. Dopa Drops give us the boost we need to tackle an annoying task.
Apex allows you to stay in a peak mental state so that you can continue to stay focused on the task longer. Apex increases mental stamina and focus, enhances neurogenesis, and allows us to stay positive and optimistic.
Beyond time management: Why we really procrastinate and how to finally stop. Ambition & Balance. Published March 7, 2016. Accessed February 7, 2023. https://blog.doist.com/overcome-procrastination/
Some people are born with great verbal fluency, while others need to invest a great deal to achieve the levels of verbal fluency they desire. Having great verbal fluency can take you very far in life with public speaking, sales, relationships, and networking, etc, so it’s an aspect of cognitive function worth investing in.
For example, the legendary NFL commentator Jim Nantz can talk continuously during the game without the need to pause and think about what to say afterwards. On the other hand, an extremely nervous student presenting to class may struggle to find the right words, stuttering, and pausing with a bunch of “umms” and “ahhs” in front of an audience. You have probably seen both examples in real life and wondered what makes them different.
What is verbal fluency?
Verbal fluency describes your ability to produce words quickly and accurately when speaking or writing. In other words, verbal fluency determines the ease with which you can access your mental vocabulary and choose the appropriate words. The better your verbal fluency is, the better you can deliver your message competently, with minimal hesitation and a great deal of trustworthiness.
#1 Vocabulary
The very first ingredient of verbal fluency is having a large mental vocabulary to choose words from. These words can be either phonemic or semantic.
Phonemic fluency allows you to recall words that begin with a specific letter. For example, try to list as many words as you can that begin with the letter “P” within a minute. You might be able to generate more words at the beginning of the test than toward the end of it. This is normal.
Semantic fluency involves recalling words that belong to a certain category. For instance, with “fruits”, you might say “banana”, “apple” or “grapes”.
The phonemic and semantic fluency tasks described here can give us an idea of one’s fluency level. While there is no one right grade on these tests, the higher your score, the better your verbal fluency will be.
Bear in mind that verbal fluency goes beyond producing words–it also involves other mental processes. This brings us to the second ingredient of verbal fluency which is executive function.
#2 Executive function: brain processes and regions involved in verbal fluency
Executive function (EF) is your brain’s ability to regulate thoughts and guide your behavior toward a goal. Just like how you can be reading this article now, checking your phone, replying to some messages, and thinking of what to eat for dinner, you are using your EF. You are focusing your attention on reading, juggling multiple tasks, and controlling your impulses to order a pizza rather than cooking a healthy dinner!
To have verbal fluency, you have to access your word store, search it for a word that fits the category, avoid repetition, and be quick. These processes are all part of your executive function, which you need to achieve better verbal fluency.
In order for you to produce words, you activate multiple brain regions depending on the task requirements.
In a neuroimaging study involving 505 healthy individuals, phonemic fluency relied mainly on the activation of the left frontal lobe of the brain, particularly the prefrontal cortex. Whereas, the left temporal and parietal lobes mediated semantic fluency. This distinction in activating brain regions in different fluency tasks is not coincidental. Phonemic fluency tasks rely mainly on executive function and thus, the frontal lobe. Semantic fluency requires the additional step of searching within the vocabulary store in the temporal lobe to retrieve a word in a specific category.
How do brain neurotransmitters contribute to verbal fluency?
To carry out the EF processes needed for verbal fluency and to achieve the required brain activity, neurotransmitters come into play. Neurotransmitters are brain messengers that help neurons communicate and relay messages. They can be:
Excitatory, having stimulating properties like glutamate
Inhibitory, which inhibit neuronal activity like gamma-aminobutyric acid (GABA)
Glutamate is the major excitatory neurotransmitter, whereas GABA is the major inhibitory neurotransmitter. Therefore, their balance in the brain is critical for supporting your verbal fluency. Excess glutamate can over-excite and kill neurons through excitotoxicity. GABA is the neurotransmitter that keeps glutamate in check and prevents excitotoxicity.
Glutamate
Glutamate (Glu), the major excitatory neurotransmitter in the brain, contributes to our learning process, memory formation and EF needed for verbal fluency. Thus, Glu is present mainly in brain regions responsible for the aforementioned functions such as the cerebral cortex, hippocampus, and thalamus.
GABA
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter that reduces the excitability of neurons. If your brain was a “car”, then GABA would function as the “brakes”. This messenger is responsible for your feelings of relaxation and calmness.
In addition to its calming effect on the brain, GABA is crucial for faster information processing and normal cognitive function.
For the best verbal fluency, you need all three GABA functions, including:
To be relaxed and in the flow
Faster information processing
Healthy cognitive functions
A few studies confirmed the positive effects of high GABA in the following brain regions on verbal fluency and cognition:
In the cerebellar hemisphere, higher GABA was associated with better performance on two verbal fluency tasks, the semantic fluency and the Controlled Word Fluency test, in 21 healthy individuals.
In the middle frontal lobe, higher GABA was linked with better overall cognition, tested by the Montreal Cognitive Assessment test in 94 healthy adults.
In the frontal lobe, higher GABA was linked to fewer distractions and better focus in 12 healthy adults..
These studies show the importance of increased GABA inhibition during verbal fluency tasks and cognitive processes. Inhibitory neurotransmission in the prefrontal cortex may partly explain why acute alcohol consumption improves verbal fluency
Dopamine
Dopamine (DA) is mostly known as the “pleasure” neurotransmitter and it is a part of the reward system in your brain. As such, DA is involved in reward processing, motivation, decision-making, and movement. Importantly, DA mediates verbal fluency performance by affecting the connection between the frontal lobe and the striatum, known as the cortico-striatal loop.
In a clinical trial, 20 healthy elderly subjects took Piribedil (50 mg), a drug that acts like dopamine, for two months. These subjects did better on the phonemic verbal fluency task compared to 20 volunteers who did not take it. These results are consistent with reduced fluency in older people due to dopamine decline. This also correlates with the decline in working memory and higher cognitive functions.
Brain glutamate, GABA, and dopamine tend to decrease with age, which may account for some age-related cognitive decline. Thus, supporting brain health is needed to preserve your mental abilities and strengthen an existing weakness in a certain domain like public speaking abilities.
How to improve verbal fluency with food and supplements
Now that you understand what verbal fluency is and how brain regions and NT come together to make it happen, here are neuroscience-based ways to improve verbal fluency.
GABA
GABA is naturally present as an amino acid in many vegetables and fruits such as:
Spinach
Potatoes
Broccoli
Chestnut
Apples
Grapes
Several clinical studies have administered GABA as a food supplement to healthy individuals and tested their beneficial effects on brain activity and mental skills.
13 healthy individuals with a history of acrophobia (fear of heights) received 100 mg of PharmaGABA, a type of GABA supplement produced by natural fermentation. The participants experienced increased relaxation, which allows the brain to concentrate and focus better. The researchers detected the relaxation in the brain as increased alpha waves, which occur when you are awake and quietly resting or meditating. These healthy individuals also had decreased beta waves, which are present during stressful situations, where you have to focus and solve a problem.
Cacao and chocolate
Did you know that chocolate and GABA can improve flow during stressful situations.
12 healthy individuals who ate 10 g of GABA-enriched chocolate before a math task, recovered from the task stress faster than those who did not have any. This simply means that eating GABA-rich chocolate helped the participants shift from a stressful state during the math task to a normal state.
Food supplements and brain boosters in the form of “nootropics” have been a favorite for many students and professionals who want to boost their brain function, while maintaining a healthier diet. It is another route you can follow to enhance your verbal fluency skills.
Aniracetam
Aniracetam is a fat-soluble product that can modulate AMPA receptors in the brain. This nootropic can enhance memory and learning. Aniracetam works by enhancing the function of the neurotransmitter acetylcholine. Additional effects include increasing oxygen consumption in the brain.
Tyrosine
Tyrosine is an essential amino acid that provides a building block for neurotransmitters such as dopamine, norepinephrine, and epinephrine. These neurotransmitters can be depleted when we are exposed to stressful situations.
Supplements such as tyrosine can help replenish this pool of three neurotransmitters and restore the mental energy to create alertness and focus. For example, whey is a protein that’s rich in tyrosine and is formed as a byproduct of cheese formation. 101 healthy individuals who took 1 g of whey protein supplement for 12 weeks performed better on the semantic fluency test, compared to subjects taking a placebo.
Rhodiola rosea
Rhodiola, or golden rose, is an adaptogenic herb that can support energy, improve mood, and balanced stress response. 8 participants received 200 mg of Rhodiola rosea before and after lunch over 14 days. These participants reported a reduction in their stress, anger, and confusion. The effects of this medicinal plant are mediated by changes in dopamine and serotonin levels, which can boost mood and promote relaxation.
Curcumin
Curcumin is a flavonoid extracted from turmeric. It acts as a neuroprotector and can improve mental function. It also increases BDNF, supporting neurogenesis. 80 individuals with ages ranging from 50-80 years, took 80 mg of curcumin for 12 weeks. The participants showed improved working memory and reduced fatigue and stress. Another study followed 2734 participants who regularly consumed curcumin-rich curry for 4.5 years. Participants who consumed curcumin more than once a month performed better on the verbal fluency task compared to others who did not.
Planning and practicing
By taking the time to practice and plan, words come to you easily. Planning can take several different forms, such as rehearsing, taking a video of yourself while talking, and through imagined interactions. With these steps, you can ensure that words will flow confidently and fluently and will improve verbal fluency.
By rehearsing for a topic, the silent pauses often filled with “ums” will be greatly reduced. You will also be training your mental dictionary, especially semantic fluency. This enables you to easily access words covering the topic of your speech or presentation.
Taking a video of your speech and watching it again, can improve both your presentation skills and verbal fluency. Judging yourself can be helpful sometimes! This strategy will give you greater control over your speech and will help you avoid surprises during the real deal!
Imagined interactions can reduce fear and anxiety associated with public speaking. This exercise is about imagining a future conversation with others. Through creating cognitive scripts in your mind, disfluencies can be reduced and your speech performance will improve. You will be able to directly address the anxiety and nervousness that may arise from the anticipated encounter, and thus reduce it.
Conclusion
Verbal fluency is a highly sought-after aspect of cognitive function that can take you very far in life. So, it’s worth investing in both in terms of practicing and supplemental support. Take our Nootopia Quiz today to identify your neurotransmitter patterns and find out which stack works best for you.
Cooper JR. Neurotransmitters. In: Smelser NJ, Baltes PB, eds. International Encyclopedia of the Social & Behavioral Sciences. Elsevier; 2001:10612-10619.
Glycine is also a key ingredient for glutathione, making it crucial for detoxification and antioxidant defenses. In this article, we’ll cover everything you need to know about glycine and how to optimize its levels.
What Is Glycine?
Glycine is the simplest amino acid, with a slightly sweet taste. Fun fact: It got this name from the Greek word for sweet, which is ‘’glykys’’.
Glycine is a non-essential amino acid, which means your body can produce it. However, that means it’s so vital that our bodies can’t do without it. Every day, your body makes about 45 grams and you get about 3 – 5 grams of glycine from food. However, many people nowadays reap health benefits from consuming more glycine.
Pathways That Make Glycine In Your Body
Your body can produce glycine from:
Serine
Threonine
And choline
Serine is also a nonessential amino acid, which comes from intermediate products of glycolysis (our carb burning pathway). Then, a specific mitochondrial enzyme turns serine into glycine.
Threonine is an essential amino acid, meaning that we have to get it from food. Our bodies can make glycine from threonine.
Lastly, choline is a chemical compound available in certain foods and as a supplement. Metabolism of choline into glycine releases methyl groups necessary for epigenetics and several other biochemical processes.
Roles Of Glycine In The Brain
Neurotransmitter
Glycine is a major inhibitory neurotransmitter that often works closely with GABA (especially in the brainstem and spinal cord) to fine-tune nerve impulses. It also modulates the excitatory functions of glutamate through NMDA receptors.
Glycine receptors (GlyRs) are widely present across the spinal cord, where they enhance the synaptic transmission and enable motor control. GlyRs are also present in hippocampus, brain cortex, cerebellum, and brainstem nuclei.
There are five different types of glycine receptor subunits:
α1
α2
α3
α4
β
Usually two of them combine to work. The alphas can combine among each other or combine with the beta subunit.
Glycine neurotransmission requires transporters– specifically transporter 1 (GlyT1) and 2 (GlyT2). These transporters enable the reuptake of glycine from the synapse. GlyT1 occurs in glial cells, while GlyT2 occurs in neurons mostly.
Once glycine binds to glycine receptors, they quickly inhibit the receiving (postsynaptic) neurons in the brainstem and the spinal cord. These inhibitory effects can affect vision, hearing, and other sensory and motor functions.
Typically, nerve impulses happen by moving positive ions (sodium and potassium) in and out of neurons. When glycine binds to these receptors, an influx of negative chloride ions hyperpolarizes the cell, inhibiting neural transmission.
Sleep
Glycine also regulates some aspects of sleep, possibly through the suprachiasmatic nucleus and the body’s circadian clock.
In a rat study, injection and oral administration of glycine reduced core body temperature by increasing blood flow to the skin. Lower body temperature typically improves sleep.
In another rat study, glycine increased serotonin in the brain. Serotonin is a relaxing neurotransmitter and a precursor to melatonin. So, glycine may improve sleep by naturally supporting melatonin levels.
Glycine also improved sleep quality and relieved fatigue in healthy people with sleep deprivation. One study restricted 10 healthy male participants’ sleep to 25% less sleep than usual for 3 nights. Subjects received either 3 grams of glycine or a placebo. Subjects that received glycine doses had significantly lower daytime sleepiness and fatigue when compared to the control group.
Thus, glycine improves sleep and sleep quality, and it promotes relaxation by working as an inhibitory neurotransmitter.
This is one of the reasons glycine is a key ingredient in Sleep Breakthrough.
Memory And Cognition
Glutamate signaling through NMDA (N-methyl-D-aspartate) receptors is crucial for spatial memory, as well as learning. Your NMDA receptors go down with age, which might contribute to the age-related cognitive decline.
NMDA receptors depend a lot on glycine. Glycine, specifically, enhances NMDA transmission and slows desensitization within NMDA receptors.
A study involving students (average age around 20 years old) and men (average age around 58 years old) aimed to investigate the effects of glycine on attention, memory, and mood. Participants received Bioglycin, an active form of glycine.
Older men had significantly lower memory and attention than the student group. However, glycine improved memory in both groups, with limited effects on attention and focus.
These results occur via the NMDA receptors, which plays a role in the basis of learning and memory.
In a rat study, glycine helped with memory and cognitive enhancement after these were impaired with D-galactose.
The researchers divided 64 rats into 4 groups (16 mice per group):
D-galactose for 60 days (100 mg/kg body weight)
D-galactose and glycine for 60 days (1 g/kg body weight in 0.9% saline solution)
Glycine for 60 days
0.9% saline solution for 60 days (control group)
D-galactose induced oxidative stress in the mice, which then threw off inflammation, damaged neurons, and impaired their memory.
Glycine inhibited these negative consequences of D-galactose because group 2 (D-galactose + glycine) had significantly better cognitive performance than group 1 (D-galactose only).
Glycine upregulates antioxidant proteins, memory-related presynaptic proteins (synaptophysin, syntaxin, postsynaptic density protein), and downregulates inflammatory proteins in these neurons.
There is no evidence that glycine can treat any brain diseases in humans currently. However, based on this study, glycine may help protect neurons, cognitive function, and memory from day-to-day oxidative stress.
Brain Development
Glycine receptors (GlyR) help your brain develop during embryonic development. For an immature central nervous system, glycine acts as an excitatory neurotransmitter which induces spontaneous activities in neural networks.
When you were in the womb, glycine enhanced the growth and maturation of:
Neural circuits
Hippocampus
Brainstem nuclei
Auditory system
Spinal development
Information Processing
Glycine receptors participate in information processing– both motor and sensory. Generally, glycinergic receptors enable sensory pathways such as hearing and vision, but also movement.
Glycine Roles In Cells And The Body
NOTE: The diseases and disorders mentioned in the following text are complex, and glycine only takes part in these pathways. We are not suggesting that glycine or supplements that affect glycine levels can cure any disease.
Building Block Of Protein And Collagen
Glycine, being an amino acid, builds up proteins. Approximately 80% of available glycine goes towards protein synthesis.
Furthermore, glycine is one of the building blocks of collagen, the most abundant protein in your body. Glycine occurs at every third position in collagen, and keeps collagen helices together.
Glycine is also necessary for the production of:
Heme: a protein that carries iron in your red blood cell
Primary bile salts: helps break down fat droplets in your intestine
Purines: a component of your DNA, ATP, and many other signaling molecules in your body
Creatine: an amino acid crucial for strong bursts of energy production and cognitive function
As an amino acid building block for enzymes, glycine makes the active site of an enzyme more flexible. This is necessary to induce conformational changes during catalysis. This may make the enzyme more flexible for many different types of substrate.
Helps With Detoxification As Part Of Glutathione
Glycine is a building block of glutathione, along with cysteine and glutamate. Glutathione is a crucial antioxidant throughout your body, especially for liver detoxification.
Glycine protects the liver from certain toxins, especially alcohol. It slows down the stomach’s ability to empty itself of alcohol, which subsequently reduces damage due to alcohol to your body. Additionally, glycine reduces the levels of metabolic products of alcohol and lowers the negative effects of oxidative stress on the liver.
Protects The Stomach Lining And Gut Health
Extensive research supports the idea that glycine is cytoprotective and helps protect the stomach lining against stomach acid.
Glycine also manages cells and linings of the gastrointestinal tract. It protects the damaged gut cells from cell death (apoptosis). Also, glycine plays a role in regenerating the intestinal lining.
In the intestines, there are several membrane transport pathways which depend on glycine. In this case, glycine increases the uptake of nutrients by cells of the intestines. Furthermore, glycine can mitigate gut irritation and damage.
Promotes A Balanced Inflammatory Response
Glycine possesses several inflammation-balancing and immunomodulatory properties. For example, it inhibits macrophages, reducing their pro-inflammatory cytokine secretions.
Many types of white blood cells release their inflammatory substances through changes in the cell membrane and intracellular calcium levels. Glycine may modulate inflammation by stabilizing their cell membrane and increasing intracellular calcium level.
Glycine also acts on neutrophils and lymphocytes, resulting in immunomodulation.
Cardiovascular And Blood Sugar Benefits
People with obesity, heart health risk, nonalcoholic fatty liver disease, and insulin resistance/type 2 diabetes, tend to have lower plasma levels of glycine.
Glycine supports healthy insulin secretion and glucose tolerance. Glycine is not a cure for these conditions, but these studies indicate the importance of glycine for cardiovascular health, as well as physiological metabolic functions.
Muscles
Glycine stimulates mTOR signaling, which has muscle-building effects. As a precursor of creatine, it also prevents muscle loss.
What Happens When Glycine Levels Are Too Low Or Too High?
Glycine is so essential that excessive or true deficiencies are very rare. However, many people nowadays benefit from supplementing with glycine, since typical glycine consumption is low relative to other amino acids.
Physiological glycine levels range from 200 to 300 µmol/L. Low circulating levels of glycine correlate with several metabolic disorders:
Non-alcoholic fatty liver disease. Patients diagnosed with this disease have 9-13% lower plasma glycine levels.
Insulin resistance and diabetes. Plasma levels of glycine in obese individuals with insulin resistance or diabetes are 10% lower than the physiological value. Additionally, low glycine levels increase the risk of developing diabetes type 2.
Oxidative stress. Glutathione is an antioxidant. Lower levels of glycine correlate with lower levels of glutathione, enhancing the consequences of oxidative stress.
On the other hand, when glycine is too high, other disorders might arise:
Nonketotic hyperglycinemia. This is a genetic disorder which disables glycine breakdown. As a result, glycine accumulates primarily within the brain, resulting in neurological consequences.
Stomach problems. If you take too much glycine, vomiting and nausea might occur.
How to Increase Your Glycine Levels
Food Rich In Glycine
The best way to naturally increase your glycine levels is to consume glycine-rich foods. Some of the options are:
Meat, especially tougher cuts, tendons, and organ meats
Fish
Gelatin-rich Bone broth that gels when it cools down
Dairy products
Legumes
Gelatin
Food Rich In Threonine
Since threonine is a glycine precursor, increasing your threonine levels can induce the same effects in glycine levels. Foods rich in threonine include:
Eggs
Meat
Nuts
Cheese
Soybean
Glycine Supplements
You can get pure glycine as a powder that dissolves easily in water and has a natural sweet taste. If you take glycine as a capsule, it usually needs a lot (>3) of capsules, so it’s best to get a powder and dissolve it in water.
Continue reading to find out more about noradrenaline and how to naturally balance your norepinephrine levels.
What Is Noradrenaline And How Is It Made?
Norepinephrine, both a neurotransmitter and hormone, enables different types of cell signaling across the brain and the whole body. The signaling works via adrenergic receptors, and noradrenaline binds to three types of them: alpha-1, alpha-2, and beta-1 receptors (it binds poorly to beta 2 receptors).
Noradrenaline basically comes from tyrosine, an amino acid. It is a non-essential amino acid, which means that your body can produce it (from another amino acid – phenylalanine). Tyrosine can cross the blood-brain barrier, and reach the presynaptic neurons. There, conversion of tyrosine to DOPA takes place, which then becomes dopamine. Your neurons then convert dopamine to noradrenaline.
Roles Of Noradrenaline In The Brain
Mood
Since norepinephrine is a neurotransmitter, its role touches upon many psychological processes, one of them being mood. Many studies demonstrate a clear connection between noradrenergic system dysfunctions and mood disorders.
Functional imaging studies show a change in sensitivity of alpha-2 adrenergic receptors in individuals diagnosed with severe depression. Additionally, noradrenaline transporter proteins have lower binding affinities in depressed patients than in the control group.
Noradrenaline can actually boost your mood. The transmission signal reaches other cells and enables proper cell-to-cell communication. One study included 43 depressed patients to determine the effects of a noradrenergic drug. Participants experienced improvements in 10 symptoms after the treatment, including increased interest and the sense of pleasure.
Keep in mind that depression and other mood disorders involve many contributing factors, and norepinephrine is only one of them. We’re not suggesting that any supplement, including ones that increase norepinephrine, can treat any disease. Every case is different so it’s best to see your physician for diagnosis and treatment.
Attention
You’re so into your work that no external noises can distract you. This is partly because of norepinephrine – it regulates selective attention.
One study focused on noradrenaline’s role in emotional regulation of attention. The study consisted of three experiments, and participants received their doses orally.
The first experiment included 36 individuals (18 women and 18 men). They received either a 100mg placebo pill or 40mg of an adrenergic receptor blocker. Participants performed the Attentional Blink Task 90 minutes after receiving the dose.
The second experiment had 30 participants (15 women and 15 men). The doses that they received were either a 100mg placebo pill, 40mg of the adrenergic receptor antagonist (blocker), or 4mg of a selective noradrenaline reuptake inhibitor (which increases noradrenaline). They did the Attentional Blink Task 120 minutes after receiving the dose.
Lastly, the third experiment involved 30 subjects (15 women and 15 men) which received either a 100mg placebo pill, 20mg of the adrenergic receptor antagonist, or 40mg of an adrenergic receptor antagonist that cannot cross the blood-brain barrier.
The blockage of adrenergic receptors significantly decreased the detection of targets during the test, meaning that attention spans changed when compared to the placebo group.
On the other hand, the selective noradrenaline reuptake inhibitor resulted in enhanced attention compared to the control group.
Lastly, the antagonist that is unable to cross the blood-brain barrier had no effect on attention, just like the placebo pill.
These results demonstrate the importance of noradrenaline in selective attention. Higher noradrenaline levels enable increased focus and attention.
Memory
Noradrenaline is crucial when it comes to memory. A study on domestic day-old chicks investigated the effect of norepinephrine on memory by training them not to peck a specific bead.
The chicks received different injections containing either adrenergic agonists or antagonists. Additionally, injection administration occurred in different time slots (before or after the training). The results revealed the importance of norepinephrine in short, intermediate, and long-term memory formation and maintenance. Increased noradrenaline release correlates with enhanced memory.
A clinical study including 30 women and 30 men researched the role of noradrenaline in arousal-induced memory. Arousal-induced memory is selective: it selects important information related to an outstanding event, while ignoring less important information.
Participants received either 40mg of beta-adrenergic receptor antagonist, or a placebo pill. Individuals that received the antagonist experienced an inhibition in arousal-induced memory, compared to the placebo group. These participants had reduced ability to select important information. This shows that norepinephrine boosts memory linked to arousal.
Sleep And Wakefulness
Noradrenaline also plays an important role in the sleep-wake cycle and feeling energized. During sleep, levels of noradrenaline significantly decrease. This decrease plays a role in dreaming: it allows our brains to process dreams, but reduces the chance of remembering them.
On the other hand, higher levels of noradrenaline correlate with wakefulness. When you wake up in the morning, your noradrenergic neurons activate.
Researchers conducted a study with zebrafish to determine the role of noradrenaline in the sleep-wake cycle. Zebrafish with a mutation in the gene that encodes dopamine beta-hydroxylase (an enzyme that converts dopamine to noradrenaline) produce an inefficient protein. Therefore, they do not produce enough noradrenaline.
These mutants display significantly lower activity when awake, during both daytime and nighttime. Additionally, they sleep 185% more during the day and 57% more during the night than the wildtype control group.
Executive Function
Executive function includes the working memory, attention, impulse control, and cognition, among other processes. The effects of norepinephrine touch all aspects of the executive function.
These connections occur because norepinephrine regulates arousal and cortical activity during executive function performance. And, since noradrenergic receptor activation depends on the arousal level, noradrenaline has a role in balancing the cognitive processes that contribute to the executive function.
Noradrenaline enables task switching. In the case of low noradrenaline activity, you may struggle to switch between different tasks.
On the other hand, higher norepinephrine activity correlates with an enhancement in reversal learning. The basis of this model is learning to make a discrimination, and then reversing the choice. For example, an individual learns to select for black color in a black-white task, and then learns to choose white instead of black color in the same task type. Additionally, high noradrenaline relates to the ability to inhibit the response to distractions.
Fight Or Flight Response
The ‘fight or flight response’ makes our body prepared for stressful or dangerous situations. As the name itself suggests, it either makes us ready to fight the danger, or flee away from it.
Norepinephrine, along from the adrenal medulla, comes from sympathetic nerve endings and triggers certain changes within our bodies during dangerous events. During these situations, norepinephrine levels rise.
This increase in noradrenaline induces higher cardiac output, relaxes smooth muscle tissue, and increases blood glucose and fatty acid levels. All of these enable us to have enough energy and an appropriate physiological state to respond to danger.
Roles Of Noradrenaline Outside The Brain
Noradrenaline is also a hormone. Its secretion from the adrenal gland induces different physiological changes via blood transport.
Blood Pressure Regulation
A study on conscious and anesthetized cats focused on the role noradrenaline plays in blood pressure control. Administration of noradrenaline resulted in increased blood pressure. Furthermore, the study highlighted the mechanism of action of alpha and beta adrenoreceptors. Alpha receptors possess both excitatory and inhibitory action, while beta receptors are of excitatory nature. They are an important part of the central blood pressure control.
Another study focused on humans and the importance of the noradrenaline transporter (NET) gene. A total of 92 individuals diagnosed with resistant hypertension participated. NET inactivates noradrenergic signaling by taking up the released noradrenaline.
A single nucleotide polymorphism in the NET gene correlates with higher norepinephrine levels in the plasma. This contributes to the resistant hypertension.
Stress Response
Stress response is finely tuned with several physiological mechanisms. Similarly, noradrenaline plays a role in stress response.
The central dogma of the stress response is increased noradrenaline release. Arousal-induced memory, or fear memory, only works with high levels of noradrenaline. Prolonged and repeated stress situations lead to symptoms of anxiety, caused by high norepinephrine levels.
Fat Burning (Lipolysis)
Norepinephrine correlates with fat burning. In adipose tissue, for example, noradrenaline induces lipolysis, as well as enhanced blood flow. This is not the case for all tissues. In skeletal muscle, noradrenaline just decreases the blood flow, but has no effect on lipolysis.
Furthermore, dopamine and noradrenaline reuptake inhibition might have an effect on mild weight loss. Bupropion is the reuptake inhibitor for both noradrenaline and dopamine.
In one study, mice received daily doses of it for 7 days. Inhibition of norepinephrine and dopamine reuptake (which increases noradrenaline and dopamine) resulted in increased energy expenditure. However, the mice didn’t eat more, move more, or produce more heat. The combination of these consequences lead to mild weight loss.
Neurotransmitters That Balance Noradrenaline
Since norepinephrine comes from dopamine, we can conclude that dopaminebalances norepinephrine production. However, some aspects of these two neurotransmitters counteract each other. For example, in a difficult feat that requires tenacity, the reward from dopamine may keep you going, while noradrenaline tempts you to quit.
Our brain constantly seeks balance. Thus, when dopamine levels are too low or too high, the brain leans towards an optimum amount.
Therefore, too high dopamine levels might lead to too high noradrenaline levels.
Signs Of Too High/Too Low Noradrenaline
Noradrenaline controls wakefulness, attention, and many other physiological functions.
Here are some signs of too high levels of noradrenaline:
High blood pressure. We need high blood pressure in dangerous situations. However, hypertension might occur if noradrenaline levels are always too high.
Hyperactivity. Norepinephrine induces wakefulness and makes you feel energized. Too much noradrenaline can lead to hyperactivity and insomnia.
Panic attacks. When noradrenaline levels are high, arousal and alertness peak. Prolonged and too much alertness might cause panic attacks.
Euphoria.
Excess sweating.
Irregular heartbeat
Signs that noradrenaline is too low:
Lack of energy. Noradrenaline influences wakefulness and regulates the sleep-wake cycle. If noradrenaline is too low, you may feel tired.
Bad mood. Low amounts of norepinephrine correlate with inability to transmit the necessary signals properly. The result can be low mood and a lack of motivation and enthusiasm.
Inability to pay attention and focus. Many studies found that low norepinephrine levels make it hard to focus.
Natural Ways To Increase Noradrenaline
1. Healthy Sleep Habits
Noradrenaline is an important part of the sleep-wake cycle. If you balance your cycle, your noradrenaline levels will likely follow the same trend.
Getting enough quality sleep is crucial for waking up refreshed and full of energy. Optimize your sleep schedule to increase your noradrenaline levels in the morning.
2. Tyrosine Or Dopamine Rich Foods
Tyrosine, and thus dopamine, are norepinephrine precursors. Utilizing tyrosine and dopamine rich foods in your diet will help to increase your noradrenaline levels.
Some of the foods rich in tyrosine and/or dopamine are:
Chocolate
Bananas
Peanuts
Yogurt
You can also turn to tyrosine supplements. N-acetyl L-tyrosine (amino acid with an acetyl group added, also called acetyl L-tyrosine) boosts dopamine and norepinephrine levels. N-acetyl L-tyrosine can better enter the brain than tyrosine and provides the building blocks for dopamine and noradrenaline. However, by providing building blocks, it tends not to have the same effects as drugs that block the reuptake of these neurotransmitters.
3. Caffeine
Caffeine is a central nervous system stimulant, meaning that it increases alertness and focus. The possible underlying mechanism of this could be noradrenaline.
One study involved 24 healthy individuals. There were 4 groups:
Clonidine/caffeine
Clonidine/placebo
Placebo/caffeine
And placebo/placebo
The clonidine doses were 200 micrograms, and the caffeine doses were 1.5 mg/kg. Clonidine is an alpha receptors agonist, and therefore reduces norepinephrine levels.
The consumption on clonidine impaired alertness, reduced blood pressure, and significantly reduced eye movement and some performance aspects. On the other side, caffeine fixed many of these reductions and impairments. It increased alertness, eye movement, and blood pressure. The results suggest that caffeine has its effects due to the noradrenergic pathways and the increase in plasma noradrenaline levels.
4. Exercise
Physical activity can increase your noradrenaline levels as it globally boosts all neurotransmitters in a balanced manner.
One study included 6 men who performed exercise with one leg, while the other leg rested. The exercise lasted for 10 minutes. The blood results showed that noradrenaline levels were significantly higher in the exercising leg when compared to the resting one.
5. Vagus Nerve Stimulation
One study involved 31 rats. The left side of the vagus nerve in the study group received a stimulus, and corresponding norepinephrine levels released in the amygdala were recorded. This lasted for approximately 2 hours, and the collection of the brain fluid samples occurred every 20 minutes.
After the first 20 minutes, noradrenaline levels significantly increased (71% higher). This increase was even more prominent at the end of the stimulation, where noradrenaline levels were 128% higher than the original physiological levels. No changes occurred in the control group who did not receive a vagus nerve stimulus.
6. Rhodiola Rosea
This adaptogenic herb helps to balance norepinephrine levels with the regulation of the stress response.
A rat study dealt with obese animals and the potential of R. rosea to help the weight loss. The combination of Citrus aurantium and Rhodiola rosea showed 10.5% lower feeding need in rats when compared to the control group. Furthermore, this administration resulted in increased norepinephrine levels (15% higher) and dopamine levels (150% higher) in the hypothalamus.
7. Phenylethylamine
Beta-phenylethylamine is an amine that influences noradrenaline levels indirectly. Specifically, phenylethylamine increases dopamine levels in neural synapses. Noradrenaline comes from dopamine, so higher dopamine levels may lead to an increase in noradrenaline levels.
Natural Ways To Decrease Noradrenaline
1. Healthy Stress Processing
Stress causes norepinephrine release. Therefore, when you’re really under a lot of stress, your norepinephrine levels tend to peak. However, chronic stress leads to lower noradrenaline levels due to reduced sensitivity of the stress-response system.
Avoiding stress completely is impossible. Instead, healthy stress processing will help with a lot of imbalances, as well as norepinephrine levels.
Healthy ways to manage stress, such as meditation and self-care, can help lower your adrenaline to healthy levels.
2. Melatonin
Since noradrenaline is very important for the sleep-wake cycle, and especially wakefulness, melatonin can produce the opposite effect.
Higher levels of melatonin will suppress noradrenergic receptors, and induce sleepiness.
3. Green Tea
A rat study investigated the effect of green tea on the secretion of noradrenaline. Rats received 50mg/kg body weight of the green tea extract for 10 weeks. Noradrenaline levels in these rats significantly decreased.
Norepinephrine really does play a central role in some physiological mechanisms. Keeping your noradrenaline levels in balance applies to many health benefits, like attention, healthy sleep patterns, and executive function.
Have you considered optimizing your noradrenaline and dopamine levels to support your focus, motivation, and mood?
Nootopia’s personalized nootropics support all neurotransmitters, including noradrenaline, naturally and in a balanced manner. We do so by providing building blocks for your body to make its own neurotransmitters, so the effects are very gentle and there are no side effects.
Click here to learn more about Nootopia stacks.
Note: Our products are not approved to treat or cure any disease and this article is meant for educational purposes only. We include the drug studies in this article as they demonstrate the functions of noradrenaline, but our products are not these drugs and are only intended for optimizing cognitive functions in healthy people. Please see your physician about treating and diagnosing diseases, especially with medications.
Tsirlin A, Oo Y, Sharma R, Kansara A, Gliwa A, Banerji MA. Pheochromocytoma: a review. Maturitas. 2014;77(3):229-238. doi:10.1016/j.maturitas.2013.12.009
Aldenson R. Stimulating the vagus nerve: memories are made of this. Apa.org. Published 2004. Accessed October 27, 2022. https://www.apa.org/monitor/apr04/vagus
It is a free radical, meaning it is a molecule with unpaired electrons. Most free radicals get a bad rap, but not NO. Nitric oxide plays a crucial role in every cell in your body!
Nitric oxide is a critical component of many biological processes in your cardiovascular, immune, and nervous systems. Just think, without proper circulation, your body can’t function, and that’s how vital NO is!
Physiologically, nitric oxide serves as an important neurotransmitter and neuromodulator. It helps you store your long-term memories and controls sleep, appetite, body temperature, and the production of neurohormones. Pathologically, when maintained at appropriate levels, nitric oxide helps to mediate some brain damage.
Roles of Nitric Oxide In The Brain
Neurogenesis
Nitric oxide plays a vital role in your body’s ability to grow and develop new neurons, or neurogenesis. Why does this even matter? You have an abundance of diversity in neurons in your brain. Each type of neuron is unique and specific to the structure and connection required by its brain region. To maintain optimal brain performance, your body must replace damaged neurons.
Alzheimer’s progression
Nitric oxide has a three-fold role in the progress of Alzheimer’s disease. To better understand how it works, you should first understand the three different types of nitric oxide synthase:
Neuronal (nNOS), which produce nitric oxide in neurons
Inducible (iNOS), which produces nitric oxide that mediates inflammatory responses
Endothelial (eNOS), which produces nitric oxide that dilates the blood vessels and increases blood flow
Now, back to what happens in the brain with Alzheimer’s. First, lower blood flow reduces eNOS. Second, plaque formations between neurons cause chronic inflammation and activate iNOS. Finally, changes in calcium receptors increase the activation of nNOS.
Oxidative stress is one of the earliest pathological changes in individuals with Alzheimer’s. In states of inflammation, nitric oxide increases considerably and contributes to oxidative stress.
With age and other pathological processes, nitric oxide can become harmful. This occurs when it reacts with another oxide and forms peroxynitrite. Peroxynitrite can then react with tyrosine proteins beginning an irreversible process leading to the accumulation of misfolded proteins that contribute to the onset of Alzheimer’s disease.
While it is clear that nitric oxide is involved in the progression of Alzheimer’s disease, scientists are unsure whether it plays a neuroprotective or neurotoxic role overall. Regardless, nitric oxide’s ability to increase blood flow can help decrease plaque growth.
Central blood pressure regulation
Central blood pressure is the pressure seen by the aorta and the blood pressure exposure of your brain, heart, and kidneys. The aorta is the biggest blood vessel that receives blood each time the heart beats.
The Central Nervous System (CNS) controls blood pressure through nerves and hormones. Special nerve endings, called baroreceptors, are located in blood vessels near the heart and act as sensors for the brain. They detect how stretchy the blood vessel walls are. Blood vessel walls stretch as blood pressure increases, activating baroreceptors.
So how does nitric oxide play into all of this? As I told you before, Nitric oxide synthase produces NO. This synthase acts throughout the central nervous system and controls the baroreceptor pathway.
Nitric oxide in your central nervous system, mainly your brain stem, is crucial to activating the sympathetic nervous system. The sympathetic nervous system regulates your blood pressure, and when there is too much activity, it can cause high blood pressure. This is why stress can increase blood pressure.
Roles of Nitric Oxide Outside The Brain
So far, we’ve talked about how nitric oxide works in the brain, but it is in nearly every cell in your body! It plays a significant role in your cardiovascular system. NO regulates all of your blood flow and tissue oxygenation. It even plays a role in your erection (of the penis and clitoris).
Blood pressure
Nitric oxide produced in the lining of the blood vessels acts as a messenger. It tells your blood vessels to either widen or dilate and contract or relax, like an elastic band. When your blood vessels widen, this allows more blood to flow, lowering your blood pressure.
As you age, your body begins to produce less nitric oxide. With less nitric oxide, your blood vessels cannot relax as easily to allow more blood to flow. Having contracted blood vessels reduces the amount of blood flow throughout the body and can lead to high blood pressure and less blood flow to vital organs. Luckily, there are ways to help counteract this through diet and exercise. Read on to learn more.
Circulation
Nitric oxide allows for more blood flow and increases the circulation of blood throughout your body as well as the brain. This has implications in many areas of your life. NO supports your body’s ability to:
Maintain oxygen flow throughout the body to maintain proper functioning of the heart, lungs, muscles, and kidneys
Fight off diseases by circulating your immune system’s white blood cells throughout the body.
Support healthy organs through circulation’s ability to remove excess waste such as carbon dioxide.
Increased circulation could mean better workouts and decreased time before muscle fatigue. NO ensures that your muscles get the necessary blood flow you need to complete your optimal oxygen-rich training. Good blood flow helps fight lactic acid build-up by flushing out lactic acid and fills your muscles with nutrients. Additionally, because NO protects against inflammation, it’s essential for tissue injury recovery.
Optimal nitric oxide levels could also mean increased endurance (yep, even in the bedroom) due to increased blood flow to the penis. The release of NO triggers the erectile response. But this is nitric oxide’s only role. NO is continuously released to sustain the erection by relaxing the blood vessels and allowing more blood.
Neurotransmitters That Balance or Potentiate Nitric Oxide
Nitric Oxide doesn’t work alone. Some neurotransmitters work to balance your NO levels and increase its effects.
Acetylcholine
Acetylcholine stimulates the release of nitric oxide in multiple ways. Within blood cells, it activates the release of NO, and in your skin, it increases the bioavailability of nitric oxide. Just under the surface are blood vessels. Acetylcholine and nitric oxide work together to dilate these blood vessels.
Glutamate
Glutamate is at the beginning of a particular pathway that activates the release of nitric oxide into the body. The proper functioning of this pathway is critical for learning and memory.
These two neurotransmitters also work together in reproduction. Glutamate activates NO, which causes a surge in gonadotropin releasing hormone, which occurs pre-ovulation in women.
Norepinephrine
Women are not the only ones who benefit from nitric oxide in reproduction. Both men and women are affected by norepinephrine’s stimulation of NO release. The release of nitric oxide occurs in the hypothalamus, which then triggers the release of the hormone Luteinizing hormone releasing hormone (LHRH). LHRH then causes the pituitary gland to make and secrete luteinizing hormones which cause testicles to produce testosterone and ovaries to make estrogen and progesterone.
Oxytocin
Interestingly, the same reaction that can induce an erection also causes yawning. Oxytocin increases the release of nitric oxide outside the hypothalamus triggering the behavioral response.
In connection to norepinephrine, oxytocin stimulates the release of the luteinizing hormone responsible for reproduction. It does this by stimulating nitric oxide synthase (what produces nitric oxide) via norepinephrine.
Supplements That Increase Nitric Oxide
Some supplements can help increase your nitric oxide levels. They work by providing nitric oxide synthase, a substrate or substance, to turn into nitric oxide, thereby increasing the amount of nitric oxide in your body. The following amino acids work together to promote nitric oxide production.
Arginine AKG
Amino acid L-arginine is the primary substrate needed for optimal nitric oxide production, and it metabolizes into l-arginine alpha-ketoglutarate (AAKG).
In a study of 24 strength-trained individuals, subjects received either AAKG + creatine, AAKG + placebo, placebo, or nothing over eight weeks. Arginine levels peaked around 2 hours and 4 hours, meaning the ideal time for supplementation is two hours before your workout. Compared to other groups, subjects who took AAKG + creatine or AAKG+ placebo experienced increased strength. Therefore, AAKG supplementation significantly increases strength. This increase is likely due to the increase in Nitric oxide production and its ability to widen the blood vessels and increase blood flow to the muscles during exercise.
Supplementing with AAKG is not only beneficial to exercise. Because it supports the synthesis of nitric oxide in cells on internal and external surfaces of the body and the circulatory system, AAKG supplementation can benefit your circulatory system and organs.
DL- Citrulline Malate
Citrulline is an amino acid that turns into arginine. Watermelon has the highest naturally occurring amount in food. Because arginine breaks down quickly, getting it into your blood supply is more challenging. This is where citrulline comes into play! Supplementing with citrulline helps arginine to stay in your blood plasma longer and could result in increased blood flow and exercise performance.
DL citrulline malate is citrulline combined with malic acid, a chemical found in fruits and wines. Malate helps to boost energy by supporting cell energy generation. Having more cellular energy allows you to exercise longer!
DL-citrulline malate is effective in both men and women to improve weightlifting. The combination of citrulline and malic acid works not only to increase arginine, thereby producing more nitric oxide, but also to reduce lactic acid.
In a study across six gyms in Spain, 41 men took part either in the control group or a group receiving a single 8 mg dose of citrulline malate. Subjects who received the citrulline malate completed more barbell bench press repetitions and significantly less muscle soreness. Therefore, citrulline malate increases athletic performance.
If both arginine AKG and DL-Citrulline Malate successfully improve your body’s performance, imagine if you combined them. You can find these amino acids in Nootopia’s unique formulas: Nectar X and Power Solution.
Nitric Oxide Supplement Side Effects
So, what about nitric oxide supplements? Are they safe? For the most part, yes, but there are some side effects you need to be aware of. Mild side effects include:
Stomach pain, bloating, or heartburn
Nausea
Diarrhea
Lightheaded or dizziness
Headache
Heart palpitations
Are there some cases where you should avoid nitric oxide supplementation? You may want to avoid NO supplements if you have or are at risk of:
Developing cancer
Cirrhosis of the liver or scarring
Low blood pressure
A heart attack
Guanidinoacetate methyltransferase deficiency
As always, talk to your doctor or qualified medical professional with any questions regarding your health.
Are there ways to tell whether your nitric oxide levels are too high or low? Yes, there’s a test for that. You can do it at home using nitric oxide test strips or ask your doctor about taking an exhaled nitric oxide test. But how would you even know if you might have an issue with your nitric oxide level? Read on to find out.
Signs of Too High Nitric Oxide
Here’s what to look out for as signs that your nitric oxide levels are too high:
Irritation of the eyes or blurred vision
Headaches or migraines
High levels of nitric oxide can also cause damage on a cellular level. When damage at this level occurs, it is associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.
Signs of Too Low Nitric Oxide
How do you know when it would be beneficial to increase your nitric oxide levels? The following symptoms are associated with low levels of nitric oxide:
Decreased blood flow
Poor circulation, such as cold hands and feet
Sexual dysfunction or lack of stamina
High blood pressure
Memory loss (also a possible warning sign of dementia)
Chronic fatigue
Sleep issues or insomnia
Low stamina and endurance during exercise
Slower exercise recovery times
Chronic stress
So, you’re experiencing one or more of the symptoms listed above. How can you treat it naturally?
Natural Ways To Increase Nitric Oxide
Eat your way to higher nitric oxide levels
Eat foods that are high in nitrates
So you’re telling me to eat nitrates? You’ve heard warnings about eating too many nitrates and that they can cause cancer. Let’s clear something up. It all depends on what type of nitrate you eat.
Harmful nitrates are those found in processed meats like bacon and hot dogs. These nitrates convert into nitrosamines in the stomach when combined with stomach acid. Nitrosamines are known to potentially cause cancer.
Where can you find the good kind of nitrates? Here is a helpful list of vegetables with the highest levels:
Dark leafy greens like swiss chard, kale, spinach, arugula
Vegetables in the brassica family such as bok choy, cabbage, mustard greens, cauliflower, kohlrabi, and broccoli
Beets
Carrots
When you eat these foods, the good bacteria in your mouth and your saliva play essential roles in the conversion process. Some nitrates are converted in your mouth by bacteria and absorbed by the stomach and intestine. The remaining nitrates are reabsorbed by your salivary glands and later excreted in your saliva.
How you eat your veggies matters. Cooking them reduces the amount of nitrates available, so it’s best to eat them raw for maximum nitrate benefits. However, you’ll still get some nitrates and other health benefits even if you eat them cooked.
Eat Foods High In Citrulline
Remember citrulline? The amino acid turns into arginine and helps keep arginine in the blood plasma long enough for it to convert into nitric oxide. Increasing foods high in citrulline helps support this process. Here are some great options:
Watermelon
Nuts
Squash
Chickpeas (eat more hummus!)
Cucumbers
Pumpkin
Increase Your Antioxidants
Antioxidants increase nitric oxide synthase activity, thereby increasing the amount of nitric oxide in your body. Here are some really important ones:
Vitamin C
Supplementing with vitamin C and addition to a nitrate-rich diet may boost nitrate levels even more. In a study of 20 healthy adults, taking a nitrate supplement along with vitamin C lowered blood pressure and stiffness of the arteries compared to a placebo group. Therefore, the combination of nitrates and vitamin C increased the nitric oxide levels in the body.
Polyphenols
Eating a diet high in polyphenols boosts nitric oxide levels in plasma and has been associated with low blood pressure. This is where it gets delicious. Good sources of polyphenols include:
Red wine
Dark chocolate
Tea
Berries
Extra virgin olive oil
Make Some Lifestyle Changes
Exercise
Exercise increases nitric oxide production. In a study of 184 individuals, one hour of aerobic exercise daily for a month increased NO levels, reduced blood pressure, and increased antioxidants in the body. So get out there and get moving!
Sunlight
Get outside and soak up some rays! Exposure to UVA radiation from the sun can help release nitric oxide into the skin. What’s even better is that the effects last for days!
Limit antiseptic mouthwash usage
Your oral bacteria is essential in maintaining your nitric oxide levels. Using antiseptic mouthwash destroys the entire microbiome. Avoid using mouthwashes labeled as antiseptic or containing ingredients like chlorhexidine, alcohol, or hydrogen peroxide. Why not try oil pulling to improve oral health?
Natural Ways To Reduce Nitric Oxide
We’ve discussed many ways to increase nitric oxide, but what if your levels are too high? How can you reduce it? To reduce nitric oxide levels, the body must slow down nitric oxide synthase. Below are some ways to do this.
L-lysine Supplementation
Nitric oxide depends on arginine for production. L-lysine inhibits the cellular transporter of arginine. Increasing your lysine levels can help slow down the production of arginine and, thereby, nitric oxide.
Increase your fat intake
Saturated fats are known to deplete nitric oxide levels. But not all fats are created equal; a lot can depend on what fats work best for your particular body type. Read more here.
Pass the salt
Increasing salt intake decreases nitric oxide production. It does this by inactivating nitric oxide synthase in your blood cells.
The Takeaway
Maintaining healthy nitric oxide levels is crucial to your health. Essentially, every part of your body needs it to thrive. From your head to your toes, nitric oxide supports healthy blood flow throughout the body, ensuring the health of your organs. NO can improve your workouts and recovery time and even keep you going in the bedroom. There are many natural ways to balance or enhance your nitric oxide levels. One of the most effective ways is by taking Nootropics. But first, find out what kind of neurotransmitter support you need the most with our quiz here.
Lion’s mane, or Hericium erinaceus, is an edible mushroom which is a part of traditional Asian medicine. It’s the most popular mushroom for its nootropics and neurogenesis benefits. In this article, we will cover everything you need to know about lion’s mane, from benefits to side effects.
What is Lion’s Mane mushroom?
Lion’s mane (Yamabushitakeor hou tou gu) is an important medicinal and culinary mushroom in oriental cultures. This mushroom grows mostly on dead or old trees in Asia and across North America. Since it is white in color and has dangling spines like a beard, it is relatively easy to recognize it on the hardwood trees.
Historically, Lion’s mane has been an important remedy in Chinese and Japanese traditional medicines. This mushroom is nutritive to lungs, spleen, liver, kidneys, and the heart. Asian cultures also believe that it enhances digestion, helps with ulcers and gastritis, as well as general weakness and insomnia.
What are Lion’s mane’s active substances?
Many polysaccharides in the cell walls and fruiting bodies of lion’s mane have medicinal benefits. For example, heteroxyloglucans, galacto-xyloglucans, xylans, and glucoxylans inhibit cell growth and cause apoptosis (cell suicide) in abnormal cells. Other polysaccharides reduce oxidative stress and protect cells from premature apoptosis.
Terpenoids are smaller hydrocarbons with lower molecular weights. There are two classes of terpenoids unique to lion’s mane, hericenones and erinacines. These two easily cross the blood-brain barrier to support and protect neurons. Additionally, they induce nerve growth factor synthesis.
Other chemicals in lion’s mane, corallocin A, hericerin, isohericenol, and N-de-phenylethyl isohericerin increase brain-derived neurotrophic factor in rodent neurons in test tube studies.
All Hericium erinaceus extracts can inhibit the growth of some bacteria, such as Staphylococcus aureus (MRSA) and Salmonella in test tube studies.
Generally, lion’s mane is a great source of nutrients necessary for proper brain functioning, but also for other vital organs and functions.
Brain, mental health, and cognitive benefits of Lion’s Mane
Brain, mental health, and cognitive benefits of lion’s mane include:
Boost mood
Improves focus
Helps with learning
Support a calm and flow state
Improves brain cell regeneration
Helps with memory
The following is how lion’s mane deliver these brain benefits.
Counteracts age-related cognitive impairment
Age-related cognitive impairment can arise due to:
Increased in inflammation
Reduced neurogenesis
Reduced ability to refold proteins correctly
Increased oxidative stress
Mitochondria dysfunction
Nutrient deficiencies from reduced appetite and poorer digestion
Lion’s mane may mitigate many of these age-related physical and mental decline.
A study included 30 Japanese women and men, aged 50 to 80, with mild cognitive impairment. There were 2 groups – one that received four tablets containing 96% of lion’s mane dry powder, 3 times a day for 16 weeks; and the other group received a placebo. Both groups then underwent cognitive tests, which measured verbal, drawing, visuospatial, and construction abilities.
The lion’s mane group were on a significantly higher level on the cognitive function scale than the control group. Furthermore, the scores increased the longer the subjects consumed lion’s mane. However, cognitive scores dropped significantly 4 weeks after the intake of Hericium erinaceus stopped. Nevertheless, these results show that lion’s mane can help mild cognitive impairment.
In one study, mice received lion’s mane extract over the course of 30 days. Lion’s mane reduced the formation of plaques and enhanced the formation of new neurons and the connections between them.
A rat study researched the role of polysaccharides found within lion’s mane, and their possible neuroprotective effects. Rats received 250μg/ml of lion’s mane polysaccharides, which induced higher cell viability, prevented cell shrinkage, and degradation.
Additionally, a mice study investigated the role of lion’s mane in learning and memory deficits. Mice received 10μg of amyloid β, which induces cognitive impairment, and ate a diet based on lion’s mane for 23 days. The results demonstrated that lion’s mane prevented spatial short-term and visual recognition memory deficits caused by amyloid β. These findings support the idea that lion’s mane reduces cognition-related issues associated with amyloid β. However, we still need a human trial to confirm this benefit of lion’s mane.
Improves acetylcholine
Acetylcholine is one of your most important neurotransmitters for cognitive functions, memory, and brain health.
Furthermore, lion’s mane enhances acetylcholine concentrations in blood and hypothalamus in mice. The mushroom polysaccharides work by increasing enzymes that produce acetylcholine. This mechanism is different from many other cholinergic nootropics which work by inhibiting the enzyme that breaks down acetylcholine. Therefore, lion’s mane combined with other cholinergics may have additive effects on brain acetylcholine levels.
Also, by enhancing nerve growth factor, lion’s mane preserves and stimulates the growth of the basal forebrain’s cholinergic neurons.
Protects and supports the growth of hippocampal neurons
The hippocampus is your brain’s memory center. It tends to shrink in adults with mood issues. Animal studies suggest that lion’s mane may help with mood by enhancing neurogenesis in the hippocampus.
A study involving male mice focused on the effect of lion’s mane on mood. One group received a lion’s mane dosage, 20 or 60mg/kg body weight, once a day for four weeks, while the other group received saline of the same amount and duration. They found that a lion’s mane enhanced the formation of new neurons and synapses within the hippocampus. Behavioral tests also showed that the lion’s mane group moved and explored more, and had better mood and motivation amidst stress.
Supports healthy neurotransmitter and inflammation balance
Day to day stress can throw off neurotransmitters and increase inflammation in the brain. These can reduce cognitive function, energy levels, motivation, focus, and mood.
In mice, ethanolic extract of lion’s mane high in erinacine A seems to support mood and cognitive functions through neurotransmitter and inflammation balance.
Mice received 100, 200, or 400 mg/kg body weight of the extract once a day for 4 weeks. Two weeks into the study, they received restraint stress for 2 weeks. The control group was not exposed to these protocols, nor lion’s mane.
Stressed mice typically move less in water and when held from the tail, while exploring more in elevated plus maze tests. Along with these behaviors, their dopamine, serotonin, and norepinephrine levels drop as their inflammatory cytokines like tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) increase.
Animals that received the mushroom had increased levels of dopamine, serotonin, and norepinephrine, as well as decreased TNF-alpha and IL-6. They also had increased brain-derived neurotrophic factor levels. These results were especially significant in groups that received 200 and 400 mg/kg body weight.
These results suggest that lion’s mane may support mood by promoting neurotransmitter and inflammation balance.
Stimulates neurotrophins
Neurotrophins are proteins that support the survival, growth, and function of neurons. There are many of these, but two of the most important ones are brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). BDNF is important for learning, memory, mood, and deep sleep. NGF supports sympathetic, sensory, and cholinergic neurons in the forebrain.
Cell-based studies show that lion’s mane constituents increase NGF and BDNF production.
In a placebo-controlled study involving 30 menopausal women, lion’s mane effectively boosted mood, reduced irritability, sleep, and wellbeing. The authors speculated that the lion’s mane helped by boosting nerve growth factor.
In a study in overweight/obese patients, 77 volunteers received lion’s mane. The lion’s mane extract didn’t significantly boost their blood BDNF, but it did boost their precursor to BDNF levels in the blood. The subjects also had improved mood, calmness, and sleep.
Support neuronal repair and regeneration
Day-to-day stress and elements can create minor damages to the nervous system. Lion’s mane supports the repair of neurons and other cells in the nervous system.
Having in mind the detrimental effects of nervous system injuries, neural re-connections are of huge importance. A study using dissociated chick embryo cells from the brain and spinal cord investigated the importance of lion’s mane for neurite outgrowth. 50µg/ml lion’s mane extract caused increased neurite outgrowth in the brain (by 20.47%) and in the special cord (by 22.47%).
Another in vitro study aimed to investigate how lion’s mane affects myelination, the process which makes insulating myelin sheaths to surround the axon. The lion’s mane extract promoted faster myelination, which started earlier than in the control cells.
A rat study focused on lion’s mane polysaccharides. Rat cells received doses of either lion’s mane extract, or nerve growth factor and brain-derived nerve factor. The results showed enhanced growth of adrenal nerve cells and neurite outgrowth, which was even higher than by nerve growth factor or brain-derived nerve factor.
Improves sleep
Lion’s mane can uniquely help with sleep. It’s not a sedative but it improves sleep quality through supporting brain balance.
A study involved 77 overweight individuals who experienced mood or sleep problems. Participants received oral lion’s mane supplement for 8 weeks, which resulted in a reduction of mood and sleep issues. They also had increased pro-BDNF levels.
One study included 8 female students who took 6 lion’s mane tablets a day, over a 4 week period. Based on a self-administered survey, lion’s mane supplementation improved their sleep quality and the general feeling of wellbeing.
Other health benefits of lion’s mane
Animal and cell-based studies have demonstrated many benefits of lion’s mane, although clinical evidence is still missing for a lot of them. Please note that we include this information for educational purposes only. We’re not suggesting that lion’s mane can treat any conditions. It’s not approved to treat or diagnose any conditions. Please see your doctor for appropriate diagnosis and treatment.
Inhibits bacterial growth
Hericium erinaceus is also an effective agent against bacteria. It works against gram-positive and gram-negative bacteria.
It successfully kills Helicobacter pylori and Staphylococcus aureus Thus, the lion’s mane is a great antibacterial agent.
Nourishes and protects the digestive tract
Lion’s mane protects and strengthens your digestive tract. First off, lion’s mane nourishes and protects your spleen and liver.
Furthermore, lion’s mane strengthens the stomach barrier protection against acid.
Promotes heart health
Lion’s mane can also be beneficial for your heart and cardiovascular system.
Lion’s mane can thin the blood. Hericenone B, found in lion’s mane ethanol extract, inhibits collagen-induced platelet aggregation. However, it did not inhibit any other platelet aggregation pathway, like thrombin. Extensive research on rabbit and human platelets supports this.
Oxidized low-density lipoprotein (LDL cholesterol) is very bad for cardiovascular health because it’s more likely to harden the arteries. A study showed that a hexane extract of lion’s mane inhibits the oxidation of LDL cholesterol. This is one of the ways that lion’s mane can help your cardiovascular health.
A high-fat diet is a risk factor for the development of many cardiovascular diseases in mice, which is equivalent to a human junk food diet. A mice study aimed to investigate the role of lion’s mane in fat metabolism. Mice ate a high-fat diet for 28 days. One group received a daily dose of lion’s mane, while the control group received the high-fat diet only. The group that had lion’s mane incorporated into their diet had 27% lower triglyceride levels and 42% less weight gain than the control group. Thus, lion’s mane promotes fat metabolism and healthy blood lipids, and somewhat protects your cardiovascular system from poor diet.
Improves cellular antioxidant defense
Oxidative stress is essential in many situations, but too much of it can be bad. For example, it can cause fatigue, interfere with cognitive function, and contribute to many diseases.
Lion’s mane activates cellular pathways that counteract oxidative stress. In a mice study, lion’s mane extract adjusted the synthesis and processing of nitric oxide, superoxide dismutase, and malondialdehyde within serum.
In another study, scientists investigated the antioxidant properties of multiple mushroom species, including lion’s mane. The antioxidant index described antioxidant potentials. Lion’s mane is among the top three species with strongest antioxidant capabilities, having an antioxidant index of 17.7%.
One more mice study dealt with lion’s mane effect on hippocampal neurons treated with hydrogen peroxide. The hot water extract of Hericium erinaceus significantly increased the activity of antioxidant enzymes and viability of neurons treated with hydrogen peroxide, as well as decreased the amount of reactive oxygen species.
Boosts your immunity
Our immunity is the primary shield against different bacteria and viruses. Lion’s mane might have a beneficial effect even on your immune system.
One mice study researched the immunomodulatory effects of lion’s mane. This mushroom improved both cell-mediated and humoral immunity, meaning killer cells and antibody efficacy. These properties are likely related to the lion’s mane ability to regulate gut mucosal immune barrier.
Apart from the adaptive immunity covered by the previous study, lion’s mane also enhances innate immunity. Mice injected with Salmonella species had 4 times longer lifespan if they also received lion’s mane extracts. This increased resistance to bacterial infections comes from stronger immune activation.
Promotes a balanced inflammatory response
Lion’s mane, like many other medicinal mushrooms, support both immune system readiness and balance. It often helps balance excess inflammation from the modern diet and lifestyle and aging.
Obesity and unhealthy metabolism can contribute to chronic inflammation. Lion’s mane counteracts excess inflammation from macrophages in fat tissues.
In a mouse model of gut inflammation, 200 and 500 mg of lion’s mane extract mitigates the inflammation and protects the gut barrier. As a result, the animals had less digestive symptoms.
Similar results are visible within microglia, where lion’s mane extracts have anti-inflammatory activity and reduce neurotoxicity in the brain.
Support healthy blood sugar control
Several animal studies show that lion’s mane can improve blood sugar control. It inhibits α-glucosidase, an enzyme that breaks carbohydrates down, slowing down carbohydrate absorption. Also, lion’s mane may also help with blood sugar by balancing inflammation, counteracting oxidative stress, and supporting other aspects of heart health.
A study included rats with diabetes, who received 100 or 200mg/kg body weight of H. erinaceus extract for 28 days. The results showed that lion’s mane decreases blood glucose level and increases serum insulin levels.
However, clinical studies regarding this benefit of lion’s mane are lacking, so it’s unclear whether lion’s mane can reliably improve blood sugar in humans.
Lion’s mane side effects
Lion’s mane is generally recognized as safe. However, be aware of contraindications and the following side effects.
Allergies
If you have mushroom or fungi allergies, you should definitely avoid consuming lion’s mane.
A 63-year-old man sought hospital care 4 months after consuming lion’s mane, where he got severe acute respiratory failure diagnosis. He also had very high levels of lymphocytes, which might indicate an allergic reactions.
Beware of your allergies before consuming lion’s mane.
Slow blood clotting
Some people benefit from the blood thinning effects of lion’s mane. However, this means it can interact with blood thinner medications. If you naturally have slow coagulation or hemophilia, you should avoid lion’s mane. Also, stop taking lion’s mane at least two weeks before a scheduled surgery.
Too much lion’s mane
Consuming too much lion’s mane can cause stomach issues.
Conclusion
Lion’s mane is a powerful medicinal mushroom with many brain and body benefits. Check out Collagenius, our potent Lion’s mane and collagen blend.
AquasparkTM is one of the formulas we use in products like GABAlicious to help improve mental focus, energy levels, and performance.
By layering stimulants with several key “brain ingredients” and central nervous system modulators, we’ve engineered Aquaspark to help you be at your best when it counts. Also, our custom stimulant blends are designed to help you stay at peak performance and alertness all day without the jitters or crashes.
Why Is Stimulant Or Energy-Boosting Activity Important In Nootropics?
Before we dive into the tremendous benefits of Aquaspark, let’s first take a second to review why nootropics can have stimulating activity on the brain, and why stimulants make up a key part of world-class nootropic stacks.
Note: here we’re talking about natural stimulants and brain boosters, not Adderall, Modafinil, or other prescription drugs.
Boosts Overall Neurologic Activity
Stimulants, when used in a safe and sustainable way, can improve overall mood and energy levels. One of the most well-known stimulants is caffeine, guzzled down by the mega-gallon in the form of coffee by people worldwide. Substances like caffeine boost neurological activity by stimulating the central nervous system and influencing other physiological parameters.
Reduces Brain Fog
Some emerging evidence indicates that nootropics may also reduce brain fog and improve cognitive function. In a placebo-controlled trial, 26 healthy adults between the ages of 20-35 were assigned to take 10 g of either a multi-ingredient nootropic or maltodextrin as a placebo. This nootropic blend, known as EvoGamers, was designed specifically for gamers. The ingredients included:
Caffeine
L-tyrosine
L-theanine
Acetylcholine precursors, including CDP choline and alpha-GPC
Acetyl L-carnitine
Huperzine A
Vitamins
Researchers then performed a variety of cognitive tests on the participants 30 minutes after they ingested the nootropics or placebo. The participants also had their heart rate and heart rate variability measured. Participants that took a nootropic blend performed better on a range of cognitive tests than the placebo group. Additionally, the group that took the nootropic supplement demonstrated higher levels of creativity and positive emotions.
Boosts Mitochondrial Function And Reduces Oxidative Stress
Stimulants can also enhance mitochondrial function, though the process by which this happens needs further exploration. One theory of how stimulants like caffeine can boost mitochondria is by promoting mitochondrial energy production. Other mechanisms include the reduction of oxidative stress, which left unchecked can damage mitochondria and other parts of the cell.
Stimulates Orexins
Orexins are neurotransmitters that promote wakefulness. Stimulants promote their transport to binding sites in the brain or upregulate their functions in other ways. Once bound in place, these orexins keep you awake, whereas blocking the receptors for orexin initiates biochemical processes necessary for sleep. Stimulants like caffeine may play a role in helping orexins perform their jobs better.
What’s The Problem With Caffeine?
Caffeine has several health benefits, but it also has its fair share of drawbacks. While caffeine is a very efficient neural activity stimulant, its effect does not always have the desired duration. Moreover, caffeine’s aggressive stimulant activity can actually stress the body and interfere with sleep.
Short Or Problematic Pharmacokinetics
One of the primary disadvantages of caffeine is its short pharmacokinetic action within the body. Caffeine absorbs into the body very quickly, with 99% of caffeine completely absorbed by the body within 45 minutes of ingestion.
After absorption, caffeine has a 2.5-4.5 hour half-life depending on the individual, meaning it’s only keeping you energized for a few hours max. However, the residual amounts of caffeine in your system can still keep you from falling asleep 9 – 12 hours after you drink your last cup. Even if you do fall asleep, it could interfere with your sleep quality.
Tolerance And More Fatigue From Adenosine Receptor Upregulation
Moreover, coffee lovers and people who frequently consume caffeine can build a tolerance to it, to where it no longer has the same stimulating effects. Part of this happens due to the upregulation of adenosine receptors.
Adenosine receptors help modulate various neurological and immunological functions within your body. Your brain’s endogenous adenosine causes feelings of drowsiness when bound to these receptors. Caffeine weakly blocks adenosine receptors, causing the sensation of enhanced energy and cognitive focus. Subsequently, continued exposure to caffeine will signal the cells to increase adenosine receptors, making you more tired in the long run.
Over time, drinking a single cup of coffee or energy drink cannot cover as many adenosine receptors as are available. Because of this, prolific caffeine users will often find they have to increase their caffeine intake over time or they feel fatigued. But on the flip side, prolonged exposure to high doses of caffeine leads to other side effects.
In other words, relying on caffeine to stay awake and functional is like taking a payday loan on your body. It temporarily blocks your ability to feel fatigue without addressing the root cause of the fatigue. This and increased adenosine receptors make you more tired in the long run. You’ll also need more caffeine to feel the same energy level. Most importantly, it keeps you from getting the most restful sleep you need to feel energized.
Stresses The Body By Taxing The HPA Axis
One of these side effects is the stress that caffeine causes on the hypothalamic pituitary adrenal (HPA) axis. The HPA axis controls the stress response of the body.
When caffeine enters the body, it galvanizes the different organ systems into action, including the HPA axis and therefore the stress response. Consistently elevated or even moderate doses of caffeine continually stimulate the HPA axis to produce stress hormones like ACTH and cortisol. This can be beneficial because stimulating the HPA axis can help with stress modulation.
Nevertheless, overstimulation of the HPA axis can lead to chronic stress, feelings of anxiety, difficulty sleeping, and a host of other symptoms. Resultantly, taking only caffeine to get through the day can cause long-term issues and ultimately more fatigue.
Interfere With Sleep, Especially With People With Weak CYP1A2
The stimulant activity of caffeine can severely affect sleep if taken too close to bedtime, and some people experience this effect much more intensely. The gene primarily responsible for metabolizing caffeine is called CYP1A2. People who have weaker CYP1A2 activity cannot metabolize caffeine that well, resulting in them experiencing insomnia and other symptoms.
Slow vs. Fast Caffeine Metabolizers
As already shown, caffeine tends to metabolize very quickly, and some people metabolize caffeine faster than others. This metabolism variability has a lot to do with the CYP1A2 gene.
People with strong CYP1A2 expression, and mutations that enhance that expression, tend to get more benefits from consuming coffee. These may include cognitive enhancement without the jitters and the antioxidant benefits from coffee. On the other hand, “slow” caffeine metabolizers tend to have slow caffeine breakdown catalyzed by CYP1A2.
One clinical study tested the rate of caffeine metabolism in different people with varying CYP1A2 levels of expression. Researchers found that caffeine enhanced exercise performance in “fast” metabolizers vs. slow metabolizers.
47.5% of the population are considered “fast metabolizers with strong CYP1A2 expression. About 11.5% comprise the “slow metabolizers,” with another 41% falling into the “medium” metabolizers category.
Is Caffeine A Nootropic And What Neurotransmitters Does It Increase?
While caffeine works well as a stimulant, many do not not consider it a true nootropic. This is because caffeine can increase blood pressure. A true nootropic does not affect blood pressure.
Despite its murky status as a nootropic, caffeine’s powerful stimulant activity can allow it to work synergistically with many other nootropics and neurotransmitter building blocks. Caffeine on its own increases catecholamines, acetylcholine, glutamine, and serotonin. It also decreases the availability of GABA and glycine, which are your calming neurotransmitters.
How Nootopia Overcomes The Pitfalls Of Caffeine
Caffeine possesses stimulant effects that can boost exercise performance and cognitive functions. But it also has side effects, such as interfering with sleep and stress response. So, instead of caffeine, we layer different types of stimulants with various pharmacokinetics so you can get steady cognitive and energy boosts without the same side effects.
For example, Aquaspark contains a very small amount of caffeine along with other stimulants with differing pharmacokinetics. We also include other neuromodulating compounds and brain boosters. Let’s take a deep dive into all the key players of Aquaspark:
Acetyl-L-tyrosine
As a key component of the broad spectrum Aquaspark formula, acetyl-L-tyrosine provides one of the essential building blocks for unlocking full brain potential. The production of energizing neurotransmitters such as dopamine and norepinephrine requires the amino acid tyrosine. Acetyl-L-tyrosine is a more bioavailable form of tyrosine that can easily cross the blood-brain barrier to provide a backbone for your energizing neurotransmitters.
Theanine
In any holistic stimulant formula such as Aquaspark, modulating and calming compounds can play a key role in ensuring a sustained response to stimulants. This prevents spikes and drops in attention and performance. L-theanine, a substance found in green tea, exists as one such modulator.
Theanine modulates stress and promotes calmness by increasing alpha wave production. Alpha waves are present during the resting yet awake state of the brain, and they play an important role in day-to-day brain activity. L-theanine also improves concentration by enhancing the alpha-attention effect, where elevated alpha wave activity boosts concentration.
One clinical study with 16 experimental and 19 control participants measured EEG activity after the experimental participants consumed a tea-like solution high in L-theanine. Participants who took the L-theanine had much greater alpha wave activity than the control group. Conclusively, the participants who took L-theanine found it easier to enter a resting state.
Many nootropic users have found great benefits for combining theanine with caffeine, as Mother Nature puts them together in green tea. Theanine buffers the jitters from caffeine and improves caffeine clearance, while simultaneously producing some synergistic cognitive benefits. Theanine also counteracts the brain blood flow restriction by caffeine.
Guarana
Guarana is another effective stimulant that works synergistically with caffeine. Energy drink manufacturers often combine caffeine with guarana for better stimulant activity.
Aside from caffeine, guarana also contains theobromine and theophylline, which have different half lives than caffeine [R30]. Theobromine has a 2-3 hour half life, whereas theophylline has up to an 8-hour half life. Therefore, guarana and caffeine together work synergistically for longer than caffeine alone.
Along with its stimulant properties, guarana possesses many other health benefits. In South America where it originates, locals often use it as a medicinal plant. Furthermore, researchers have found guarana to have significant antioxidant and antimicrobial properties.
Schizandrol-A
Isolated from the plant Schisandra, schizandrol-A functions as a central nervous system inhibitor, specifically by inhibiting monoamine oxidases (MAOs). MAOs are enzymes that break down neurotransmitters like dopamine and serotonin, and inhibiting them leads to higher levels of dopamine and serotonin in the brain. These neurotransmitters are known as some of the brain’s “happy chemicals,” and can improve mood and cognitive function.
Capsaicin
While not in Aquaspark specifically, capsaicin is another powerful stimulant found in our other Nootopia formulas like Noospark, often used in combination with Aquaspark. Capsaicin has selective stimulant activity upon afferent neurons is believed to enhance energy balance. It also has cardioprotective, anti-inflammatory, and digestive benefiting properties.
Bringing It All Together: Layering Caffeine With Brain-Supporting Compounds
The Aquaspark formula contains two kinds of high-quality caffeine, including coffee bean caffeine which contains high levels of antioxidants. The second source of caffeine in Aquaspark, caffeine anhydrous, provides a rapidly absorbable source of caffeine for an instant energy boost.
But taking only these sources of caffeine does not deliver the long term energy boost your body needs to get you to the next level. That’s why we’ve layered these powerful stimulants with all the ingredients mentioned above to create a sustainable source of cellular energy that will enhance your performance and health.
How It All Comes Together In Aquaspark: Best Stimulants For Sustained Energy And Brain Function
We engineered Aquaspark so that different components work synergistically together and counteract potential side effects. We also took into account the fact that the brain in high gear burns through neurotransmitters faster and generates more oxidative stress. So, here’s how everything comes together.
Guarana contains some caffeine, along with theobromine and theophylline, which have different half lives than caffeine. This allows aquaspark to improve wakefulness for longer than caffeine alone.
At the same time, theanine buffers the jitters from caffeine and improves caffeine clearance, while producing some synergistic cognitive benefits. Theanine also counteracts the brain blood flow restriction by caffeine.
Neurotransmitter support: Acetyl-L-tyrosine provides building blocks for dopamine and other catecholamines necessary for energy, while schizandrol boosts dopamine and huperzine-A boosts acetylcholine by moderating the acetylcholinesterase enzyme.
Plant antioxidants from guarana and coffee bean extract help counteract oxidative stress that may occur as you put your brain on high gear. They also protect the mitochondria, the cell’s energy source, which are critical for your brain to work clearly and improve connectivity between all areas of brain function.
Other Steps Nootopia Takes To Provide The Best Stimulants
We want Nootopians to get the best possible results out of their products. That’s why we go the extra mile to ensure that the stimulants you are getting are truly effective. Some of the ways we have optimized Aquaspark include:
Educating Users
To help Nootopians learn the absolute best routines for taking any products containing Aquaspark or other stimulants, we inform our users about caffeine tolerance. To circumvent caffeine tolerance, we recommend weekly cycling off of stimulants, so that you can let your receptors rest and avoid caffeine withdrawal.
As world-class formulators and top performers, we know that no nootropics can truly overcome sleep deprivation and unhealthy lifestyles. Therefore, we also advocate for getting the best sleep you can get to maximize the benefits you get from nootropics.
Innovative Delivery Methods
We package our high-quality stimulants in the most absorbable delivery methods. These include stimulants in forms like sippable liquid, double-layered capsules, and micronized deliveries. We want to make sure that your body absorbs the highest amount of stimulants and other essential active ingredients as possible.
Providing Building Blocks/Raw Materials For The Brain To Be Awake
When your brain is in the highest gear, it needs more building blocks. So, we include components like B vitamins and amino acids such as Acetyl-L-tyrosine in the stack along with the stimulants. This creates a formula that doesn’t just stimulate the brain, but also nourishes it to function at its best without the subsequent crash.
Formulas like Aquaspark literally provide the essential building blocks the brain needs to create neurotransmitters and other compounds in order to support wakefulness and attention.
Personalization
Finally, as with all our formulas, the ultimate goal is to help you achieve your personal God mode. We use a detailed questionnaire to get to know you and your brain before formulating your first stack. Then, each month, we take into account your feedback and hone your personal subscription box until we have a truly excellent formula you need for whatever life throws at you. Become a Nootopian today and add GABAlicious to your monthly order. If it doesn’t work for you, we have a 365-day money-back guarantee.
Omnipept-N is a custom amino acid blend targeting GABA and dopamine, micronized with a uridine monophosphate base.
Uridine monophosphate is a naturally-occuring building block of RNA. It’s an important element of your brain cells. Uridine monophosphate, or UMP, readily crosses the blood-brain barrier and can help increase choline in the brain, synergizing with many nootropic extracts and compounds. It supports the creation of new synapses, dopamine production, and phospholipid production. By doing so, UMP promotes a clear mind, motivation, mental flexibility, and enhanced learning and memory.
Together, the Omnipept-N blend with uridine monophosphate create a specialized nootropic blend that boosts memory, focus, motivation, and learning speed without overstimulation.
Omnipept-N2: Acetyl-n-tyrosine micronized with a custom amino acid blend targeting acetylcholine and serotonin.
By boosting acetylcholine, serotonin, and catecholamines, Omnipept-N2 promotes good mood, memory, drive and verbal fluency. Omnipept-N2 is a component of the inner capsule of Brain Flow, Focused Savagery, and Upbeat.
Omnipept-O
Ominipept-O comprises of triacetyluridine micronized with very low doses a custom amino acid blend that modulates acetylcholine and glutamate functions through AMPA receptors.
Triacetyluridine is a form of uridine that is better absorbed into the blood and brain than uridine. It boosts and stabilizes mood and promotes a sense of wellbeing. It also protects neurons from day to day exposures and excess glutamate. Last but not least, it possesses all the benefits of uridine and uridine monophosphate.
Together, the Omnipept-O and triacetyluridine support cholinergic-based brain function. It also supports verbal fluency and cognitive and connectivity aspects behind healthy socializing. We include Omnipept-O in Apex, GABAlicious, Mental Reboot AM, Nectar X, Power Solution, and Zamner Juice.
Omnipept-1
Omnipept-1 is a custom amino acid blend targeting acetylcholine, dopamine, and norepinephrine neurotransmission, micronized with pyroglutamic acid, glycine, theanine, and aspartic acid.
At the same time, it boosts blood flow to the brain and makes all the other nootropic extracts and compounds work more effectively.
Pyroglutamic acid is a naturally-occurring amino acid in the human body, derived from glutamine. It enhances cognitive function by increasing acetylcholine, GABA, and glycine levels. As a result, it has a net relaxation and flow state-promoting effect.
Together, the Omnipept-1 blend and other ingredients work together to promote focus and flow-state in Brain Flow and Power Solution.
Omnipept-A
Omnipept-A is a custom amino acid blend targeting dopamine (phenylalanine and acetyl-L-tyrosine) and serotonin, combined with calcium citrate.
Omnipept-A helps maintain glutamate sensitivity of your AMPA receptors, boosting focus, and concentration. By boosting brain energy (ATP and Dopamine), it also increases acetylcholine and thus improves focus, clarity, and memory.
By boosting dopamine and serotonin function, these ingredients in Omnipept-A work together to promote a calm and relaxed good mood. It also helps with verbal fluency, emotional intelligence, and socialization. Omnipept-A is a component of Focused Savagery, GABAlicious, Upbeat, and Zamner Juice.
Omnipept-P
Omnipept-P includes CDP-choline micronized with a proprietary amino acid blend targeting dopamine, GABA, and noradrenaline. It’s a component of Focused Savagery.
By increasing acetylcholine in the brain and hippocampus, Omnipept-P improves memory and understanding of complex concepts. At the same time, the right level of dopamine and noradrenaline helps with laser-like focus and vigilance. Omnipept-P also uniquely supports mood, motivation and drive without jitters or overstimulation. Lastly, by boosting blood flow in the brain, it helps improve the performance and duration of all supporting nootropics. Now that you understand how Omnipepts are, check out our nootropics here.
The good news is that you can stimulate BDNF production and boost your brain’s BDNF levels naturally. In this article, we’ll share with you how to increase your BDNF levels naturally.
19 Ways to Increase BDNF Naturally
Many ways to increase BDNF are hormeses, which are stressors that make you stronger in small and healthy doses. In response to these stressors, your brain produces BDNF to grow and adapt. In addition, you can mix and match these hormeses in order to reap even more health benefits, including greater increases in BDNF levels.
Exercise
Exercise increases neurogenesis and favorable brain responses that come with an increase in BDNF in both aged and young people.
Longer exercise sessions increase BDNF more, but even 10 minutes of intense exercise can somewhat increase BDNF and improve your cognitive function.
However, this is not a quick fix, as BDNF can fall to pre-exercise levels in 30 – 50 minutes. Therefore, to sustainably increase BDNF, you should exercise regularly. If you wish to step it up, working out in a hot room even further increases your BDNF levels than exercising alone.
Heat exposure
Hyperthermic conditioning is the process of continuous exposure to high temperatures for a short time. You can get hypothermic conditioning from any type of heat exposure, including, steam saunas, dry saunas, hot baths, and infrared saunas. Any of these heat exposures can increase your BDNF.
Infrared saunas expose the human body to as high temperatures as 60°C for at least 15 minutes, typically increasing core body temperature by around 1°C.
In addition, rat studies show that infrared lights on the brain show antidepressant and anti-anxiety effects partly by improving hippocampal neurogenesis and increasing BDNF levels.
Your BDNF levels increase either by performing exercise in a hot room, enjoying your day submerged in hot water, or relaxing in infrared saunas.
Stress management
BDNF levels decrease in response to stress, so it is important to keep your stress levels in check. Proper nutrition and exercise aid in stress management and enhance cognitive function.
Intermittent fasting
Intermittent fasting is defined as not consuming food or caloric beverages for twelve or more consecutive hours.
It reduces oxidative stress and inflammation, all of which connect to increased production of BDNF. It also helps with BDNF levels by improving blood sugar control.
Ketosis
Ketosis delivers similar anti-aging and cognitive enhancement benefits as intermittent fasting, except with more ketones to fuel the brain. Naturally, you may also enter ketosis while fasting.
When the body is in ketosis, ketone bodies aid in the production of BDNF.
A ketogenic diet decreases neuronal death in the presence of inflammation and excess glutamate. Also, ketone bodies have antioxidant and anti-inflammatory properties.
Deep sleep
Our body goes through four sleep stages, including rapid eye movement (REM) and non-rapid eye movement (NREM).
Sleep is divided into five stages:
Wake
N1 (Stage 1)
N2 (Stage 2)
N3 (Stage 3) or deep sleep
R or REM Sleep.
Stage 3 (N3) is the deepest stage of sleep. This is the hardest stage to wake up from. REM sleep enhances learning and memory. Lack of sleep in stages N3 and R lower BDNF levels.
Sleep problems affect physical and mental health, and increase stress vulnerability.
Reduction in BDNF levels is connected to poor sleep quality. Because sleep deprivation is stressful to your body, it lowers BDNF.
Sleep deprivation (along with chronic stress) may increase anxiety, insomnia, and depression. Thus, getting enough sleep for your brain and body is crucial for all aspects of health, including BDNF levels.
Sunlight exposure
Our BDNF levels tend to shift with the seasons. BDNF concentrations tend to increase in the spring and summer, while decreasing in the fall and winter. In addition to boosting BDNF, the sun increases vitamin D production and improves mood.
Only 20 minutes of exposure to natural light is enough to increase your BDNF levels. Therefore, it is important to get some sun during the day and avoid being in enclosed and dark spaces all day.
Nootropic supplements that boost BDNF
Curcumin/turmeric
Turmeric is a spice that originated in India and has been used for thousands of years. It has many medicinal properties due to curcumins and turmerones, which have antioxidants and inflammation-balancing properties.
Curcumin increases cell viability and balances inflammatory responses in the brain. Turmeric curcumin supplements increase BDNF levels and may help with mood due to these properties.
Fish oil/omega-3 fatty acids
Omega-3 fatty acids are important components of neural cell membranes and myelin sheath, which are critical for healthy neuronal signals. Fish intake or omega-3 supplementation, reduces inflammation, oxidation, and cell death. This benefits proper neuronal functioning and development.
Omega-3 (found in fish oil) enhances cognitive functioning. By decreasing oxidative stress, omega-3 maintains neuronal function and plasticity. This action increases BDNF levels.
Cacao
Cocoa contains flavonoids that can enter the brain to protect neurons and enhance cognitive function. The antioxidant and neuroprotective properties of cocoa aid in BDNF production.
Coffee fruit extract (including caffeine and teacrine)
Generally speaking, caffeine enhances cognitive function—learning, memory, attention, mood, and BDNF levels. Coffee fruit extract comes from coffee berries and contains less caffeine than the average cup of coffee. Nevertheless, coffee fruit greatly increases BDNF levels.
Theacrine is present in coffee and tea, along with fruits and herbs. It enhances cognitive functions. It also potently increases BDNF.
Green tea
Green tea contains many antioxidants with neuroprotective effects and a source of caffeine. We owe these properties of green tea thanks to the presence of polyphenol within it, particularly epigallocatechin-3-gallate (EGCG).
Green tea, especially EGCG, effectively increases BDNF levels.
Fruit polyphenols (resveratrol and polyphenols in blueberries)
Resveratrol is an important polyphenol with anti-aging and anti-inflammatory properties. Resveratrol can significantly boost BDNF levels.
Blueberries and red wine are great sources of resveratrol. However, you may need to eat 10,000 blueberries to get enough resveratrol, so supplementation is the only way to get sufficient doses to improve your BDNF levels.
Magnesium
Magnesium is important for over 300 biochemical pathways in the body, including in the cardiovascular, neuromuscular, and nervous systems. In the nervous system, it is especially important for nerve transmission and neuromuscular conduction.
Increasing brain magnesium improves memory and learning ability. Not only is magnesium mood-boosting but it also increases BDNF levels.
L-theanine
L-theanine is an amino acid with a calming effect found in green tea It has neuroprotective activity (antioxidant activity). L-theanine is a cognitive enhancer that boosts alertness, mood, and attention span partly by increasing BDNF levels.
Ginseng
Ginseng is one of the most adaptogenic herbs. Panax ginseng is the most common ginseng example.
Panax ginseng contains ginsenosides—abundant with anti-inflammatory and antioxidant properties. These properties contribute to neuroprotection and preservation.
Ginsenosides improve energy levels and promote calmness amidst stress. It also plays a role in cell viability—promotes cell survival.
Noopept
Noopept is a small peptide-like molecule similar to piracetam. It has high cognition-enhancing and neuroprotective effects, meaning that noopept increases the survival of neurons.
Noopept directly stimulates BDNF production in neurons.
Synbiotics and butyrate
Synbiotics are probiotics and prebiotics mixtures that work together to provide health benefits to the consumer. They can improve your gut flora composition better than probiotics alone.
Inflammation in the brain and low BDNF levels are linked to age-related cognitive impairment. Synbiotic supplementation counteracts these processes by increasing BDNF, promoting a balanced immune response in the brain, and increasing neurogenesis.
Butyrate is a byproduct of microbial fermentation of dietary fibers. Not only does it support the gut barrier but also increases neurogenesis and BDNF levels. Therefore, it may help with cognitive impairment.
Lithium
Lithium is also particularly well known for its ability to increase levels of BDNF. It protects neurons and reduces cell death.
Lithium stimulates hippocampal neurogenesis. It enhances cognitive functions and overall mental performance. Lithium has a remarkable influence on cells. Apart from protecting cells, it induces cellular repair and regeneration.
To learn more about BDNF, check out parts 1 and 2 of our 3-part series:
For nootropic aficionados and biohackers everywhere, brain health is of paramount importance. The blood-brain barrier (BBB) is a vital structure for brain function that influences how certain nootropic supplements can enter the brain. Whereas, if your BBB becomes leaky, it can allow inflammatory molecules and toxins to enter, causing brain fog, low mood, and other problems. Therefore, if you are looking to optimize your brain function, you should definitely optimize your BBB health.
While Nootopia supplements are spectacular for increasing brain performance levels, no supplement can address all of the root causes of BBB dysfunction. Therefore, it’s vital to learn what might be keeping your BBB – and subsequently your brain – from operating at 100%.
In this article, we’ll cover everything you need to know about the BBB and what can happen to throw it out of whack. Then in Part 2, we’ll discuss different tests that can indicate either optimal or dysregulated BBB function. We’ll also explore how to enhance your BBB function to ultimately best protect your brain.
Why Do We Have The Blood-Brain Barrier?
You probably already know that blood is absolutely essential for life. Blood brings oxygen, nutrients, and signaling molecules like hormones to every cell in your body, while removing carbon dioxide, waste, and dangerous substances.
But surprisingly, blood is actually incredibly toxic to the brain. The hemoglobin in blood can act as a free radical when it touches brain cells, rapidly causing massive damage and cell death.
So how does the brain get all the vital compounds and nutrients it needs if blood is inherently toxic to brain tissue? The answer to this conundrum lies within an incredibly intricate network of small blood vessels wrapped in layers of protective cells.
These cell and vessel networks weave together to create the blood-brain barrier, which covers almost every part of the brain. This all-important structure makes sure the brain gets the nutrients and molecules it needs.. Simultaneously, this highly sensitive network strictly controls which substances can pass into brain tissue, protecting the brain from diseases and toxins.
People who have a fully-functional blood-brain barrier (BBB) tend to have lower levels of brain inflammation and balanced levels of different vital chemicals. This results in overall improved brain function and performance. Conversely, researchers have established a link between a poorly functioning BBB and several neurodegenerative and autoimmune diseases.
What Makes Up The Blood-Brain Barrier?
Cells that form the BBB make up specialized structures called neurovascular units (NVUs). The core components of NVUs are the endothelial cells that line the blood vessels.
The tiny spaces that still remain between the cells of the inner wall of the blood vessels are tightly sealed with structures known as tight junctions. You can think of these cells with their tight junctions like a brick wall. The cells act like the bricks, and the tight junctions act like mortar. The tight junctions keep the cells tightly sealed so dangerous substances can’t get through.
Besides the cells and tight junctions, NVUs contain cells called pericytes, which attach to the basement membrane of blood vessels. Pericytes are smooth muscle cells that often spread out over several cells, and can control the diameter of the blood vessels by contracting and relaxing.
Finally, blood vessels are wrapped in astrocytic endfeet, which connect to nerve cells called astrocytes. These endfeet connections allow the brain to regulate blood flow in the BBB. They also provide a direct neural connection with the brain.
In a fully functional BBB, all of these different cells work together to make sure the brain gets everything it needs. Additionally, it prevents the brain from ever coming into contact with substances that are toxic to it.
What Happens When The Blood-Brain Barrier Is Compromised?
Unfortunately, our bodies aren’t perfect. Sometimes, even a carefully regulated system like the BBB can get thrown out of whack. Scientists and healthcare practitioners sometimes refer to this as “leaky brain,” and have identified several diseases linked to this occurrence.
Moreover, “leaky brain” has a laundry list of signs and symptoms that overlap with many other diseases. This can make it difficult to identify what exactly is happening when the BBB malfunctions.
However, damage to the BBB, and “leaky brain” onset, may arise in many brain diseases before any other symptoms emerge. This means your brain’s all-important barrier could become compromised before you even know what’s wrong.
For the most part, BBB damage tends to start with the tight junctions, which become less tightly sealed, or “leaky”. This allows substances and inflammatory cells into the brain which should not be there.
Possible Signs Of “Leaky Brain”
As explained above, researchers are still unsure whether dysfunctional BBB causes certain diseases, or if it arises as a dangerous byproduct. Regardless, several symptoms and conditions have been linked back to “leaky brain” development. Here are some potential symptoms of a dysfunctional BBB and “leaky brain.”
Please note that while many of our ingredients can help with the BBB, these conditions all have many contributing factors. Often, fixing the BBB alone doesn’t cure these conditions. Our products are not approved to treat any disease. We’re only including the links between the blood-brain barrier and these conditions for educational purposes. Please see your healthcare provider for diagnosis and treatment of any health conditions.
Brain Fog
Brain fog is a common symptom that can indicate a host of conditions. Often associated with chronic conditions like Chronic Fatigue Syndrome (CFS), researchers define brain fog as any kind of mild mental impairment. This impairment may affect concentration, memory, or cognitive ability.
While scientists still don’t fully understand what causes brain fog, they have found that brain fog is also correlated with inflammation. Because inflammation increases BBB permeability, brain fog can indicate some degree of BBB dysfunction. However, researchers are still working to establish a definitive link between brain fog and “leaky brain”.
To learn more about brain fog, what causes it, and how to address it, check out this article.
Chronic Fatigue
Everyone can experience typical fatigue when we get too exhausted and need to rest. Chronic fatigue, however, stays constant and does not improve with sleep or rest.
Researchers still do not understand what causes chronic fatigue, but many believe that BBB leakiness plays a huge role in its onset. Additionally, those with chronic diseases tend to possess compromised BBB networks.
As with many symptoms of BBB dysfunction, researchers still haven’t determined whether “leaky brain” causes chronic fatigue or simply indicates it. Regardless, “leaky brain” and chronic fatigue share a strong correlation.
Migraines
Migraines and chronic pain can arise for a variety of reasons and are linked to many different conditions. Scientists are now exploring if migraine presence indicates BBB dysfunction. Current research suggests that BBB permeability may increase during migraine attacks.
Hyperactivity And Trouble Focusing
Certain neurological disorders that affect focus and cause hyperactivity, such as ADHD and ADD, may be caused or accelerated by “leaky brain”. Research suggests that the same mast cells that cause inflammation often kickstart a vicious cycle that results in an inflamed brain.
This brain inflammation can severely affect focus and promote hyperactivity. Therefore, difficulty focusing could be a sign that the BBB has undergone some kind of damage.
Anxiety And Depression
Many people with mental health issues have brain inflammation that causes BBB dysfunction. Feelings of anxiety and depression can point to BBB dysfunction. Addressing the BBB as a core factor in treatment for these mood disorders may prove to be highly effective. However, leaky BBB is not the only factor in mental health issues, so it’s important to see a healthcare provider to get diagnosed and treated for these.
Seizures
BBB disruption can cause seizures and epilepsy. The severe neural disruption that occurs during seizures puts significant stress on the BBB. As a result, seizures could be a symptom of severe BBB dysfunction, and potentially a cause as well.
Memory Loss And Cognitive Decline
Scientists have vigorously researched the link between BBB dysfunction and the development of neurological diseases affecting memory, such as Alzheimer’s and dementia. Still, they are cautious to say that a “leaky brain” is actually causing these diseases.
So far, research points to a correlative link between memory loss as well as cognitive decline and “leaky brain”. Stress and inflammation can allow certain inflammatory proteins to cross the BBB and start to interfere with brain functions This interference can then cause problems with memory and mental acuity.
What Causes Damage To The Blood-Brain Barrier?
Research cannot yet distinguish if a physiological problem contributes to “leaky brain,” or if “leaky brain” causes that problem to begin with. As a result, medical professionals are very cautious before saying anything “causes” BBB dysfunction or “leaky brain” .
Having said that, there are some factors that have a strong connection to “leaky brain” onset:
Chronic Inflammation
Of all possible causes of a “leaky brain,” chronic inflammation hits the top of the list. Especially during systemic, or whole-body, inflammation, the BBB can become incredibly sensitive to pro-inflammatory chemicals. This creates a chain reaction that can open up the BBB, ultimately leading up to “leaky brain”.
Some of the inflammatory compounds involved in “leaky brain” include cytokines, which are immune signaling molecules that serve many important functions. However, they can also contribute to chronic brain inflammation if left unchecked. Scientists have begun exploring the role that cytokines play in the development of both neurological and psychiatric disorders.
Additionally, mast cells, the brain’s primary immune defense, can release several pro-inflammatory chemicals which can lead to BBB dysfunction. Mast cells are large immune cells that can release various inflammatory compounds. However, overstimulation of mast cells causes “leaky brain” by increasing the permeability of the blood vessels in the BBB.
Inflammation affects everything connected to the BBB, from the tight junctions of the ECs to the connections between vessels and astrocytes. If left unchecked, inflammation can wreak havoc on the BBB, and can manifest as many different conditions and diseases as a result. On the other hand, anti-inflammatory treatment can potentially restore the function of the BBB.
If you struggle with brain function and symptoms of chronic inflammation, consider seeing a practitioner to test, identify, and address the root cause of chronic inflammation.
Leaky Gut
Like so many other physiological issues and diseases, BBB damage often has its roots in gut dysfunction. This makes sense, because our gut is essentially like a second brain. The link between the digestive tract and the brain, aptly coined the “gut-brain connection,” affects nearly all bodily processes.
As a result, researchers postulate that “leaky gut” and “leaky brain” share an inextricable link. Often, BBB dysfunction carries over to the gut lining and vice versa.
Like the cells lining the blood vessels in the brain, the gut lining cells also have tight junctions. These keep the gut walls well-sealed so that food stays in while pathogens and toxins stay out. If you have genetic variants that affect tight junctions in the gut, they can also affect tight junctions in your BBB.
However, these tight junctions can also become “leaky,” increasing the intestines’ permeability and allowing food particles to end up outside the digestive tract. When this happens, the body initiates an inflammatory response to try to control the damage.
Unfortunately, the inflammation caused as a result of “leaky gut” can transfer over to the brain. Once inflammatory molecules, including cytokines and mast cell products, reach the BBB, they can cause damage resulting in “leaky brain”. If you are experiencing a “leaky brain,” you likely may already have a “leaky gut”.
Although it sounds pretty terrifying, “leaky gut” actually is reversible and treatable. To learn more about the root causes of leaky gut and how to fix it, check out this leaky gut article.
Poor Sleep
In rats, sleep restriction contributed to BBB leakiness, suggesting that sleep deprivation in humans can affect the BBB too. Researchers hypothesize that the increased permeability of the BBB occurs due to low-grade inflammation linked to sleep loss.
Furthermore, they postulate that quality rapid-eye-movement (REM) sleep may play a massive role in preserving the BBB. Lack of it can cause significant damage to the organism as a whole.
Addressing lack of sleep requires a holistic lifestyle-based approach. If you want to explore how you can start sleeping better, check out our article on how to overcome sleep deprivation.
Poor Blood Sugar Control
Our brains need a constant supply of glucose, but if this glucose supply is not carefully regulated, the BBB can suffer. Researchers observed increased BBB permeability, especially to brain-disruptive compounds, in rats that had experimentally-induced diabetes.
Furthermore, researchers found in another study that hyperglycemia, or high blood sugar levels, lowered the ability of rats and mice to recover from stroke and cardiac stress. Ultimately, blood sugar dysregulation could damage the BBB, especially in people with blood sugar-related diseases like diabetes.
Your brain weighs 2% of your body weight but uses ~20% of all glucose your cells use. So, the brain is exquisitely sensitive to blood sugar fluctuations, even if you don’t have metabolic syndrome or diabetes.
Your brain fog or mood swings from poor blood sugar control can be an early warning sign. In fact, people can have symptoms of suboptimal blood sugar control and insulin response for years before they develop a disease. To learn whether blood sugar is a problem for you, check out this blood sugar article.
Mold Toxins
Toxins from mold can seriously impair the BBB. Many mold toxins enter the body through the nose via inhalation before being swallowed into the gut. The nose has a direct connection to the brain due to olfactory nerves, making it very easy for mold toxins to cross the BBB compared to other various toxins.
Once they’ve crossed the BBB, mold toxins can damage it by altering how BBB cells interact with their surroundings. They can also increase cellular permeability and interfere with tight junctions. Some mycotoxins are even cytotoxic, meaning they can outright kill the vital cells that make up the BBB.
The World Health Organization estimates that anywhere from 10-50% of houses worldwide have the conditions necessary for mold growth. This number tends to skyrocket in low-income and developing areas.
Symptoms of mold sensitivity include respiratory symptoms such as runny/stuffy nose, shortness of breath, respiratory infections, and even pneumonia-like symptoms. If you think you may be suffering from mold toxicity, talk to your doctor about potential tests and treatment options available. Additionally, get your home professionally inspected for toxic mold.
High Oxidative Stress
Oxidative stress in the brain occurs due to increased nitric oxide (NO) and reactive oxygen species (ROS), or free radicals. Under normal circumstances, these two molecules play vital roles in cell signaling during normal brain function.
However, during oxidative stress, the brain has too much of these molecules, or the enzymes that break them down don’t work correctly. When this happens, these compounds start to wreak havoc on everything around them. This includes cell membranes, extracellular matrices, and even the very DNA inside the cells of the NVUs. Unchecked, oxidative stress starts to unravel the very fabric of the BBB.
Oxidative stress can be elevated by a variety of lifestyle factors. These include:
Smoking
Alcohol abuse
Not exercising enough
Exercising too much
Exposure to toxins
Metabolic syndrome
Poor diet lacking in antioxidants
Tension and fatigue
Age
Long-term consequences of high oxidative stress can result in a “leaky brain.” This happens because many of the processes that contribute to higher levels of oxidative stress create positive feedback loops. Essentially, this means that the molecules that cause oxidative stress are self-multiplicative, and they interfere with the very processes designed to curb them
The more oxidative stress your brain is under, the more it is going to experience in the future. This leads to more and more damage to the BBB.
Reducing oxidative stress levels in your body can be as simple as increasing your intake of antioxidant-rich foods. You can also explore exercising in a way that helps you feel your best and de-stressing as much as possible.
Homocysteine
Homocysteine is a toxic amino acid not directly involved in protein synthesis. Homocysteine is synthesized from the amino acid methionine, and as a result, appears very similar to it chemically [R42]. It does have important roles in metabolism by acting as a sulfur-storing and molecular transfer molecule for specific metabolic processes. Scientists are still working to understand all its functions within the body.
Despite its usefulness, high levels of homocysteine are harmful, and they correlate with both cardiovascular disease and increased BBB permeability.
One possible reason why elevated homocysteine wreaks so much havoc in the body is that it can incorporate itself into proteins. Since it’s so similar to methionine, it can replace it during protein synthesis, and can also interfere with the protein-folding process. When malfunctioning proteins are created as a result, they can cause damage to structures within the cell.
Subsequently, too much homocysteine can interfere with the BBB by causing cell detachment and death, which damages the ECs. High homocysteine levels also interfere with the functions of the astrocytes.
Elevated homocysteine may contribute to Alzheimer’s, Parkinson’s, depression, anxiety, and cognitive dysfunction. Scientists believe the dysfunction of the BBB plays a crucial role in the development of these diseases. However, not everyone with these conditions shows elevated homocysteine.
Elevated homocysteine can come from both genetics and lifestyle. Ask your doctor for a homocysteine test to see if it’s a problem for you.
Mental-Emotional Stress
Stress can be good for you and your brain, but too much can be damaging. Excess stress for too long can contribute to a“leaky brain”.
Stress can overstimulate the hypothalamic-pituitary-adrenal (HPA) axis, the system responsible for our stress response. The HPA axis controls levels of cortisol, which reduces inflammation. While cortisol is antiinflammatory, activating the HPA axis can also stimulate mast cells to produce pro-inflammatory chemicals.
This overstimulation of mast cells could increase BBB permeability. Long-term chronic stress can result in continual BBB disruption and “leaky brain” development.
Chronic stress and traumatic experiences can disrupt healthy nervous system function in a variety of ways. To learn more about how damaging stress and trauma can be, check out this article.
In Part 1 of this article, you’ve learned all about the blood-brain barrier and what causes it to malfunction. You’ve also learned what signs point to “leaky brain” where the BBB is no longer working optimally.
In Part 2, you’ll learn how you can test for “leaky brain.” You’ll also get some information on practical, holistic steps you can take to promote a healthy BBB, and thereby a healthy brain.
