Category: Brain Health

Without them, you would struggle to:

• Receive and process information
• Store information
• Remember information (short and long-term)

Being able to do these things helps you manage the world around us. Your cognitive functions decline naturally as you age. You might already be experiencing this. For example, how sensitive we are to sounds begins to decline at age 30.

However, you can do a lot to help support your cognitive function and stay sharp in the long run. In this article, we’re going to dig deep into the different cognitive functions and provide some tips on how to boost them. 

In this article, Part 1, we’ll explain the various cognitive functions and how they work. In the next article, Part 2, we’ll cover ways to boost your cognitive functions.

What Are The Different Cognitive Functions?

Cognitive functions are a wide range of mental abilities. Let’s dive into each one and explain how they work. 

Perception

Perception is your brain’s interpretation of the world around you. This includes all of the information you take in via your five senses. Is it the same thing as reality? No. Interestingly enough, the activity in your brain is the same when you perceive something as when you hallucinate.

Do you remember that dress that went viral a few years ago? People couldn’t decide whether it was white and gold or blue and black. That’s because how we perceive things differs from those around us. 

So what’s happening neurologically to help us perceive and make sense of the world around us? Essentially, our brains make up a story about what we experience.

Each of your senses has specialized nerve cells that turn the energy they receive into a neural signal and send it to the brain, making up a process called sensory transduction.

Two neurotransmitters identified as responsible for your perception are dopamine and serotonin, both considered “feel good” chemicals. 

In a study of 5 subjects, researchers explored the role of the dopamine and serotonin systems on perception and decision-making. Researchers recorded dopamine and serotonin levels while subjects undergoing deep brain stimulation played a computer game.

Researchers observed that while subjects were perceiving dots on a screen, serotonin levels increased in the striatum, a part of your forebrain necessary for controlling voluntary movement when you feel uncertain. Right before subjects took action, dopamine levels increased while serotonin levels decreased.

These results highlight the role of serotonin in slowing you down when you perceive information and the role of dopamine in speeding you up when uncertainty begins to fade. 

What’s also interesting about perception is that while we do see things and make decisions, we don’t process this information in the same space as we do images. Perception occurs in the forebrain, while image processing occurs in the visual cortex at the back of the brain.

Perception goes well beyond what you simply see. It’s how you process the information around you through your individual lens. 

Memory

Memory is probably the most well-known cognitive function. In its simplest form, it is the retention of information over time. It also allows you to recall information from the past and use it to understand the present. 

When you think of memory, you’re probably thinking of long-term memory. It’s this type of memory that’s most worrisome when you notice you can’t remember that person’s name or recall certain words or phrases.

There are two types of long-term memory:

1. Explicit: events and facts
2. Implicit: skills and habit – information that you gain and retrieve subconsciously

You also have short-term memory, sometimes referred to as your working memory. It’s used to store information for a brief duration. For example, memorizing the access code in your email to input the information in an app or website. 

So how do all of these memories become memories? Just like perception, it begins with the intake of sensory information. This information then travels into your prefrontal cortex where it stays for you to use as part of your short-term memory.

For memories to become long-term, your hippocampus gets involved by retrieving information from your working memory. Then from there it changes your neural wiring to hold onto the information more permanently in the cerebral cortex. The hippocampus helps you connect your various sensory experiences and a particular event. It even works to layer on connections between new and past events. 

Your brain has a particular region called the amygdala, an almond-shaped structure in the front of your temporal lobe behind your ears. The amygdala is responsible for your emotional memories. It is mainly activated when you’re presented with a threat or something that causes fear. The amygdala guarantees you remember precisely where you were and what you were doing on 9/11. 

Also central to emotional memory is your cerebellum. It was previously thought only to regulate movement memory, but more recent research determined that the cerebellum is directly connected to the prefrontal cortex. The two parts of the brain work together to correct errors in movement based on memory, like correcting your basketball shot to improve your accuracy.

Neurotransmitters that make memories happen include:

• GABA (gamma-amino-butyric-acid): critical for memory consolidation, spatial memory, and memory retrieval
• Acetylcholine: released in various areas of the brain when you experience something new or significant and when consolidating long-term memories
• Glutamate: plays a critical role in memory formation by strengthening the connection between neurons
• Dopamine: involved in the encoding and consolidation of new memories.
• Noradrenaline: primarily active in the amygdala, noradrenaline interacts with cortisol (a “stress hormone”) to support emotional memory, processing, storage, and retrieval. 

Learning

Memory and learning are intricately linked. We learn through making memories. When you learn something new, just like memories your 85-plus billion neurons begin to fire and send electrical impulses to other neurons. These electrical signals allow you to read, write, think, and play sports. 

These connections made in your brain occur because of neuroplasticity. It’s the idea that changes can occur in your brain and new connections (synapses) are made. These connections become more robust and faster through repetition. While you sleep, your brain prunes the extra or unused connections to become more efficient. 

Learning and memory use the same parts of the brain and neurotransmitters. In the scientific world, learning is generally thought of as acquiring information that changes knowledge or behavior, while memory is the storage of information.

Attention And Focus

The modern world constantly bombards us with sensory information. Sounds and colors surround us. The internet is filled with competing news stories and social media reels. But our brain has limits. Our brains use focus and attention to filter important information and ignore the rest. 

Driving your attention is either:

• Goals: known as endogenous attention, where your brain is in charge of what you’re focusing on, or..
• Stimulus: known as exogenous attention, where the external stimuli of your surrounding environment drive your attention

Your brain allows you to switch back and forth between these two types of attention and to multitask by dividing your attention between the two.

Your attention requirements change based on what you are trying to achieve. If you’re going for a walk down the street, you can let your mind wander and take in the sights and sounds around you. If you are trying to complete a work task, you’ll need to achieve mental focus or sustained attention.

Your attention system in the brain is a connected network throughout almost every lobe in your brain. At the center are three different regions:

1. Sensory regions: These include the primary auditory cortex, primary somatosensory cortex, and primary visual cortex and are responsible for processing incoming information. 
2. Parietal regions: Located in the upper back portion of your skull behind your frontal lobe, this region controls where you should focus your attention.
3. Prefrontal regions: Serves as your attention control center, particularly finding the balance between your endogenous and exogenous attention. 

What you are focusing on determines what region(s) are most activated. 

Also, these five key neurotransmitters ensure that your attention goes to where you need it most, allowing you to pay attention.

• Acetylcholine: Works throughout the brain to enhance focus by controlling neural activity across the three attention regions of the brain. It increases your neural signal based on what area of the brain requires the most activity.
• Dopamine: Helps focus your attention mainly when dealing with familiar information such as movement and emotional responses. Two different types of dopamine receptors work throughout the brain to either excite or inhibit cell activity.
• Norepinephrine: Promotes arousal or wakefulness to improve your focus or increase reaction times.
• Glutamate: Necessary for proper neuronal signaling to help maintain attention and focus.
• GABA: Plays a special role in visual attention by focusing on relevant stimuli while blocking out irrelevant information. 

Decision Making

From what to wear to what to eat to what to watch, your day is filled with decisions. And I just mentioned some you make consciously. You make other subconscious decisions almost constantly throughout the day. While various factors go into decision-making, you’ll group them into two primary ways:

• Perceptual decision-making: You gather information from the sensory information around you and use that to make decisions. For example, If you are walking down a sidewalk and another person is coming, you’ll pay attention to where you think they will go so that you can avoid that path and a possible collision.
• Reinforcement-guided decisions: You base these decisions on more comprehensive knowledge and the value of a particular action. You decide what to do based on what you believe will give you the greatest reward. 

The two most critical parts of the brain in the decision-making process are the prefrontal cortex and the hippocampus. They interact to help get you the information you need.  Researchers created an algorithm to break it down into four steps.

• Step 1: You receive sensory information from a stimulus that excites neurons in the hippocampus.
• Step 2: A secondary set of stimuli arrives in the hippocampus, producing information as a neural response.
• Step 3: The information produced in step 2 is then sent to the prefrontal cortex, which determines whether you need more information to make a decision. 
• Step 4: Finally, the prefrontal cortex makes the preferred decision, and you take action. 

Different parts of the basal ganglia also play critical roles in decision-making. Here are a few highlights:

• Nucleus Accumbens: the crucial area for reward processing. Reward drives decisions involved in this area of the brain.
• Dorsal Striatum: engaged in making decisions about movement and taking action.
• Subthalamic Nucleus: serves as a “brake” in decision-making to help prevent impulsivity.

After making a decision, your amygdala comes into play. Based on the outcome of your decision, you experience a positive or negative emotional response. The amygdala stores this information and uses it when making a similar future decision.

A study examining decision-making tracked the brain activity of participants. Researchers determined that your brain makes a decision up to ten seconds before you become aware of it. They were even able to accurately predict the decision a subject was going to make based on brain activity.

Pulling this all together are neurotransmitters. Let’s explore which ones help you make decisions. 

• Dopamine: Helps you make risk vs reward decisions.
• Serotonin: Works together with dopamine to determine risk vs reward, with a focus on uncertainty.

More recently, a study exploring decision-making focused on the relationship between serotonin and dopamine during the decision-making process. Using deep brain stimulation, researchers were able to track these neurotransmitters’ levels while subjects made decisions.

Beyond the risk vs. reward role of dopamine and serotonin, researchers learned that both neurotransmitters help you choose to act. When subjects made decisions, serotonin levels decreased, and dopamine levels increased.

• Acetylcholine: Tells you to feel uncertain about a decision when you don’t have enough information to predict the outcome.

Inhibition

Your inhibition helps you survive. It prevents you from taking impulsive action when you aren’t likely to benefit from it or if it’s not in line with your character. This extends to your thoughts and emotions as well. In some cases, you need inhibition to go off autopilot to actually do the right things, such as following instructions or driving on the other side of the road.

Green, Purple, Orange, Yellow

Caption: The Stroop test measures your inhibition skills by asking you to tell the color of the text. Most people will default to reading the text.

Those who struggle with inhibition are more likely to engage in risky behavior such as alcohol and drug abuse and risky sex. And those with overactive inhibition are more likely to experience feelings of anxiety and difficulty in new social situations.

A literature review explored the neuroscience of inhibition. Previously, researchers thought inhibition took place in one region of the brain– the right inferior frontal gyrus, part of your frontal lobe. However, they now find that inhibition includes a broad network of activity.

Researchers determined that the inhibitory network extends to the cortical and subcortical regions of the brain. These regions include the outer layer of your two cerebral hemispheres and deep into the gray and white matter. This network of connection between the frontal lobe and other brain regions is active and interacting during inhibition control.

The primary neurotransmitter involved in inhibition is GABA. GABA, known as a calming neurotransmitter, exerts the same type of influence on your thoughts and behaviors by reducing the excitability of your neurons.

Dopamine is likely involved in overactive inhibition. In a literature review exploring the role of dopamine in inhibition, researchers found that the interactions of dopamine between the prefrontal cortex and midbrain regions like the amygdala and striatum can result in increased inhibition and anxious behavior.

Spatial Orientation

One of the most complex cognitive functions is spatial orientation. It requires you to take in spatial information in your environment and make sense of it in an organized manner so that you can successfully navigate the space around you. 

This helps you get from one place to another, whether by driving over to a friend’s house or making your way to the bathroom in the dark at night. If we didn’t have these skills, we would essentially go around in circles and never make it to our destination. 

The parts of the brain responsible for spatial orientation are your hippocampus, amygdala, and parahippocampus (located just outside the hippocampus). Within these regions are special cells with neurons specific to different types of information. They include:

• Place cells: serve as a basis for cognitive maps, or maps that your brain creates to make sense of your surroundings, including specific landmarks. 
• Head direction cells: help your brain orient the exact direction of your head independently of your surrounding environment
• Grid cells: when these cells are firing, they can represent the entire spatial layout of your environment.
• View cells: focus on individual objects or people in an environment

A study examining the role of the hippocampus focused on taxi drivers as they navigated through a simulation of London streets. After undergoing MRI scans, researchers determined that compared to a control group, taxi drivers have larger hippocampuses. This demonstrates how critical of a role the hippocampus plays in spatial orientation.

The most critical neurotransmitter for spatial orientation is acetylcholine. It influences how you experience what you see and integrate that information to make sense of it. It also allows you to focus your attention on specific visual stimuli, like zeroing in on a person or object of interest.

Researchers were able to highlight the role of acetylcholine on spatial orientation by increasing acetylcholine in subjects using the drug donepezil. Compared to a control group, those with increased acetylcholine activity improved their ability to detect a target surrounded by distractions.

The same study confirmed that enhancing dopamine and serotonin levels did not increase subjects’ ability to detect the target. This further confirms the critical role of acetylcholine in spatial orientation as opposed to other neurotransmitters.

Language And Verbal Fluency

Do you ever stumble over your words, trying to recall the name of something? Or feel like you’re lost in a conversation because of the vocabulary? This is a function of your language and verbal fluency. It includes your ability to:

• Read
• Write
• Speak 
• Communicate

The language areas in the brain, located on the left side of the brain in the cerebral cortex, are aptly named after the neurologists who studied them, Paul Broca and Carl Wernicke. Broca’s area helps us recall words and speak, while Wernicke’s area decodes speech. 

While the left side of the brain is primarily used in adults, a study focused on language development in children found something different. 73 subjects took verbal and fluency tests while tracking brain activity. Researchers found that how well children perform on verbal tests relies on the right hemisphere of the brain rather than the left. This is also true for adults.

What we know about the neurotransmitters involved in language is a more recent discovery. Interestingly, scientists know less about the neurotransmitters involved in language than other cognitive functions because they cannot study language using animal models since animals don’t have language abilities. 

The neurotransmitter extensively involved in language and verbal fluency is L-Glutamate. It plays a role in accessing, producing, and comprehending language. There are four different types of L- Glutamate receptors in the central nervous system, each of which plays its own unique role in overall fluency.

The neurotransmitter GABA balances out L-Glutamate. GABA helps you slow down your speech and put pauses between your words and sentences. You can think of L-Glutamate as your language accelerator and GABA as the brakes.

Now that we’ve covered your various cognitive functions, you may also be wondering if there are things you can do to boost them and ensure that you maintain high function. Of course, there are. In Part 2, we’ll cover 8 ways to boost your cognitive functions.

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Recognized by its beautiful orange flowers, California Poppy (Eschscholzia californica) grows across North America. Native Americans utilized this plant in their daily meals and their medicine. In this article, we will cover how California Poppy improves sleep, helps you relax, and more.

Alkaloids And Their Biosynthesis

Benzylisoquinoline alkaloids are metabolites with a wide range of effects, including relaxation and discomfort relief. California Poppy plants produce these alkaloids.

Sanguinarine is a major benzylisoquinoline alkaloid originating from California Poppy. This alkaloid inhibits bacterial growth, and is even an ingredient found in toothpaste . Other alkaloids extracted from Eschscholzia californica are californidine, escholtzine, and caryachine .

WRKY transcription factors play a role in alkaloid biosynthesis across plant species. California Poppy possesses 50 WRKY genes, with different expression levels across plant parts .

Benefits Of California Poppy Seed Extract

Sleep

California Poppy seed extract can improve your sleep. In a study, mice received between 100 and 200 mg/kg body weight of California Poppy extract. Doses above 100 mg/kg induced sleep in mice .

The alkaloids act on GABA receptors. GABA is an inhibitory neurotransmitter which can promote sleep .

A study included 22 individuals who struggled with sleep. They received a maximum of 4 pills every night for a month. The pills contained 80 mg of California Poppy extract and 32 mg of Valeriana officinalis extract.

The results after one month were:

• Sleep struggles decreased by 30%
• Total duration of sleep increased by 30 minutes
• The efficiency of sleep increased from 78% to almost 85%
• Waking up during the night decreased by 25% .

30 patients with similar sleep issues received 20 drops of either Eschscholzia californica or Passiflora incarnata (passionflower) extract at bedtime for 40 days. Individuals in the California Poppy group slept 59 minutes longer than the passionflower group .

Calming Effects

California Poppy seed extract promotes relaxation. In a mice study, California Poppy extract dosage of 25 mg/kg body weight induced calm behavior .

Moreover, another study demonstrated similar results. Mice received 25 mg/kg body weight of California Poppy extract. The staircase test showed anti conflict effects in the California Poppy group. Additionally, the poppy seed group spent more time in the lit box during the light/dark choice test .

Another study included 264 individuals. One group received a placebo, and the other group received tablets containing Crataegus oxyacantha and Eschscholtzia californica extracts for 3 months. Individuals experienced significant improvement in their mood. They also reported increased feelings of calmness .

Reduces Discomfort

California Poppy seeds impact discomfort relief. A mice study showed that supplementation with this plant extract reduced discomfort in mice. Animals performed less discomfort-reducing activities, such as twitching, jerking, and stretching .

A rat study dealt with effects of California Poppy extract on discomfort perception and peripheral nervous system issues. The injection dose was between 100 and 300 mg/kg body weight.
A single dose significantly reduced discomfort perception in rats. Thermal and other stimuli had no effects on rats, as California Poppy extract inhibited the aching sensations .

Try Dream Optimizer, which contains California Poppy extract. Spray Dream Optimizer under your tongue and then swallow after 30 seconds. Feel the calming effects within minutes.

Side Effects Of California Poppy Seed Extract 

As California Poppy seed extract promotes relaxation and calmness, supplementation can cause slowed breathing and sleepiness.

In the human study, the pill containing 80 mg of California Poppy extract (and one more ingredient) caused frequent urination in one participant .

11.5% of participants who received Eschscholzia californica extract (plus another plant extract) had mild digestive issues in another human study .

Conclusion:

California Poppy seed extract is a safe and effective sleep and relaxation remedy. However, it’s not for everyone, as some people experience some side effects. When in doubt, consult a qualified naturopathic doctor before introducing a new supplement.

References:

It affects all your body functions including your brain function. It helps with neurotransmitter production, hormone regulation, detoxification, and DNA expression.

In this article, you will learn what methylation is and how it affects your cognitive health. We will also explore how you can improve your methylation to improve your brain function.

What Is Methylation? 

Methylation is a chemical reaction in which a one-carbon unit called a methyl group is added to DNA, proteins, and other molecules. Methyl group is a group of four atoms, one carbon, and three hydrogen atoms (CH3).

Depending on which part of the DNA is methylated or not methylated, specific genes can be turned on or off like a lightswitch.  In biochemistry, the word methylation refers specifically to DNA methylation. But it’s important to remember that it is part of a bigger system called one-carbon metabolism. DNA methylation is just one of the many reactions that is extensively studied within one-carbon metabolism. The ability to turn on and off genes through DNA methylation is the hallmark of epigenetics and has important implications for many diseases.

One-carbon metabolism refers to a group of reactions in which they transfer methyl groups within each other to make different compounds.  

The one-carbon metabolism consists of three main reactions: 

1. Folate cycle 
2. Methionine cycle
3. Trans-sulfuration pathway (see diagram).

In the methionine cycle, the amino acid methionine from our diet donates a methyl group to make S-adenosylmethionine (SAMe). SAMe donates a methyl group to make S-adenosyl homocysteine (SAH), which then donates to make homocysteine. 

The homocysteine is then metabolized in two ways:

1. Recycled back to methionine with the help of the folate cycle
2. Converted to cysteine via the trans-sulfuration pathway. Cysteine is one of the key amino acids that make up glutathione, your body’s most important antioxidant.

The folate cycle converts inactive folate into active methylfolate with the help of the MTHFR enzyme and vitamins B12, B2, and B6. The activated methylfolate donates a methyl group to homocysteine to recycle it back to methionine.

Your diet has a direct impact on this one-carbon metabolism and thus DNA methylation. This is because the nutrients you absorb influence the relative abundance of these methyl groups. 

Specifically, nutrients that you get from your diet, such as vitamins B2, B6, B9 (folate), B12, methionine, betaine, and choline are all methyl donor precursors in the one-carbon metabolism.

How Does Methylation Affect Cognitive Function And Health? 

Methylation affects your cognitive function by helping your body:

1. Make and activate neurotransmitters
2. Make hormones
3. And detoxify

Producing And Activating Neurotransmitters

Neurotransmitters are chemical messengers in your brain. Neurons in your brain produce them and use them to communicate with each other.

There are more than 100 neurotransmitters in your body. They can be categorized into 2 main categories:

1. Small-molecule neurotransmitters
2. Neuropeptides

We are interested in the small-molecule neurotransmitters for this article.

The 6 major small-molecule neurotransmitters are:

• Norepinephrine: Plays an important role in the regulation of attention, arousal, cognitive function, and stress reactions.
• Dopamine: This is our feel-good hormone that is involved in regulating motivation and pleasure.
• Serotonin: Your happy hormone involved in learning, memory, happiness, and cognition. It is also a precursor to melatonin, which is a hormone that helps regulate your circadian rhythm and sleep.
• Acetylcholine: The main neurotransmitter of the parasympathetic nervous system. In the brain, it’s also essential for memory and learning. Outside the brain, it’s crucial for muscle contractions.
• Glutamate: The major excitatory neurotransmitter in your central nervous system.  It plays an important role in shaping memory and learning. It is also a precursor to GABA.
• GABA: It is the primary inhibitory neurotransmitter in your central nervous system and functions to calm us down.

Methylation helps you make, activate, and deactivate these neurotransmitters.  Specifically, it is involved with: 

• Conversion of tryptophan to 5-HTP 
• Conversion of serotonin to melatonin 
• Conversion of norepinephrine to adrenaline 
• Transportation of dopamine, norepinephrine and adrenaline. 

Therefore, methylation can affect your mental health, cognitive function, and mood. 

Producing And Activating Hormones

Methylation helps to convert serotonin into melatonin.  Melatonin is a hormone that is produced in response to darkness.  It regulates your circadian rhythm.

Help With Detoxification

Methylation plays an important role in detoxifying the hormone estrogen through the liver.  The liver metabolizes estrogen by breaking it down into several intermediate metabolites.

One of these intermediate metabolites is 4-hydroxyestrone (4-OHE1).  It can be harmful if it accumulates in the body.

Thus, the body converts it to the less harmful 2-methoxyestrone (2-ME1) through methylation. It is then safely excreted from the body.

If there’s a problem with methylation, the buildup of 4-OHE1 can damage DNA and promote the growth of cancer cells.

As An Aging Clock In The Cells

Currently, DNA methylation provides biomarkers that can determine the biological age of any tissue.. Based on this information, some longevity researchers believe that the status of DNA methylation can predict life expectancy and mortality of a person.

Controlling BDNF Levels

Brain-derived neurotrophic factor (BDNF) is a protein that plays a key role in the survival and plasticity of neurons in the brain. This has implications for learning and memory.

Your diet and microbiome can influence your BDNF levels through epigenetics, including methylation.

How Does Low Methylation Affect Brain Function And Nootropics Effectiveness? 

Help Activate Neurotransmitters

Many neurotransmitters don’t cross the blood-brain barrier. The body makes them in the brain from their precursors through methylation. Therefore, Nootopia products support these neurotransmitter levels by providing the body with their precursors. You can get these precursors either through diet or supplementation. 

For example, tryptophan is an essential amino acid that you get from your diet.  It is converted into 5-HTP through methylation. 5-HTP is a precursor of serotonin, which you can take as a supplement. 

Support Healthy Homocysteine Levels

Homocysteine is an amino acid that comes from the precursor methionine in the methylation cycle. Methionine is an essential amino acid found in foods such as meats, eggs, dairy, nuts and vegetables Some of this homocysteine is then converted to cysteine with vitamin B6 as a cofactor and some are recycled back to methionine with the help of B12 and folate.  

When there’s a deficiency in one of these cofactor vitamins and when there’s low methylation, homocysteine can build up in the body and cause problems. Elevated homocysteine is unhealthy for the brain (has a direct neurotoxic effect) and blood vessels  

We can support healthy homocysteine levels by increasing methylation and by providing all the precursors and methyl donors such as:

• Vitamin B12 
• Vitamin B6 
• Vitamin B2 
• Vitamin B9 (Folate) 
• Methionine 
• SAMe 
• Betaine (trimethylglycine) 
• Choline

However, it’s important to note that these two biomarkers do not always go in a reverse relationship. It is possible to have low methylation and still have normal homocysteine levels. The body has the ability to clear homocysteine through other means.  There might also be a genetic variation that can affect homocysteine metabolism. 

MTHFR Variants And Why They May Matter 

The MTHFR gene provides a recipe to produce the enzyme methylenetetrahydrofolate reductase (MTHFR). The MTHFR is a rate-limiting (slowest) enzyme in the methyl cycle.  It converts folate into the active form of folate called L-methylfolate (5-MTHF).  

Some mutations in this gene slow down the MTHFR enzyme. Slow MTHFR often, but not always, means reduced methylation and/or methylfolate. If you have elevated homocysteine, you have low methylation. However, you can have low methylation without elevated homocysteine–it can show up as:

• Irritability
• Suboptimal cognitive functions
• Hormone imbalances
• And suboptimal fertility

There are more than 30 gene mutations for the MTHFR gene, but the two most commonly studied are C677T and A1298C. Both mutations reduce the MTHFR enzyme activity, but at varying levels.

C677T

The C677T variant substituted C to T at position 677 on the DNA recipe for the MTHFR enzyme. This results in producing a different amino acid valine instead of alanine.

If you have one copy of this mutation (heterozygous), you have 40% less enzyme activity.  But if you have 2 copies of the mutation (homozygous), you will have only 30% of normal enzyme activity left.

Although C677T has been associated with many diseases and elevated homocysteine, plenty of people can live normal and healthy lives with this variant. That’s because of epigenetics–your body can read this gene more times even if you have the weaker gene. You also have numerous other genes that can make up for the lower enzyme functions.

A1298C

The A1298C variant substitutes the amino acid glutamic acid into alanine.

Heterozygous individuals have a 15% reduction in enzyme activity, while homozygous individuals have a 30% reduction. 

Therefore, the impact of this mutation on the MTHFR enzyme activity is slightly less than the C677T variant.

This mutation is less likely to lead to increased homocysteine levels by itself.  But it can have a bigger impact when combined with the C677T mutation.

How To Improve Methylation For Brain Function

There are a variety of ways to improve methylation for cognitive function. Most people think that they can just fix the issue by taking methylfolate, when that is not always the case. The human body and brain involves an intricate balance of thousands of biochemical pathways and nutrients. 

It is important to figure out why you have an undermethylation issue. Proper testing with a health provider can help you to figure out and address the issue. 

For individuals with weak MTHFR, folic acid (especially at high doses) can further reduce methylation. Folic acid refers to a synthetic form of vitamin B9, which is more shelf-stable and inexpensive. It’s the most common form for supplementation and fortification.  

Methylfolate

Methylfolate is the activated form of folate and doesn’t require the MTHFR enzyme to get activated.  For those who have MTHFR polymorphisms, taking methylfolate bypasses this rate-limiting step.  It provides all the methyl groups the body needs. This can normalize homocysteine levels by recycling homocysteine back into methionine.

SAM-e

SAM-e or S-adenosyl methionine is a compound that is naturally produced in the body from methionine. It acts as a methyl donor for many reactions in the body. The body likes to use SAMe as the main source of methyl groups for DNA and RNA methylations. SAMe is also needed to convert epinephrine to norepinephrine, and to make homocysteine and creatine.

TMG or Betaine

Betaine or trimethylglycine (TMG) is made from choline in an irreversible fashion. It is also a methyl donor. It regenerates methionine from homocysteine in the betaine homocysteine methyltransferase (BHMT) pathway. Betaine is stored in large amounts in the liver and kidneys, where the BHMT pathway is most active. It becomes the major determinant of homocysteine levels in the blood when there’s a folate deficiency or excessive alcohol intake. 

Choline

Choline is a precursor of betaine and is another nutrient found in our diets.  It has neuroprotective effects and is found in eggs, chicken, beans, and wheat germ. Both choline and its metabolite betaine are methyl donors. They re-methylate homocysteine back to methionine. Similar to the MTHFR mutations, if you have a low dietary intake of choline, it can lead to increased levels of homocysteine. 

Riboflavin

Riboflavin (vitamin B2) is an essential vitamin. It is needed for many functions in the body including energy production and mitochondrial health.

It is a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), and acts as a cofactor for the MTHFR enzyme. 

This means that riboflavin is essential for the activity of the MTHFR enzyme. It has been shown that riboflavin is inversely related to plasma homocysteine levels.

Creatine

Creatine is an essential amino acid made naturally in the body from methionine, arginine, and glycine. Your body makes most of it and only a small amount comes from food.. In the body, it is a fuel for the brain and your muscle cells.  

You may have heard of it for its use in athletic performance and increasing muscle mass.  But it also acts as a nootropic. Nootropics are substances that can increase mental performance and cognitive function.

In the body, producing creatine uses up a lot of methyl groups. Taking creatine directly can significantly reduce this demand for methylation in the body. This frees up methionine for those with low methylation issues. 

Studies have shown that creatine supplementation may improve short-term memory and reasoning. It is most beneficial when there’s a brain creatine deficit induced by acute stressors such as heavy exercise and sleep deprivation or chronic stressors.

Food Sources Of Folate

Natural food sources of folate (not folic acid), such as chicken liver and leafy green vegetables, are excellent ways to support your methylation. They also tend to come with other methylation nutrients together in whole foods, so the risk of overdose or overmethylation are low.

Conclusion

Now that you’ve learned about methylation and how it can impact your brain function, remember to work on optimizing your methylation to optimize your brain. This is also why Nootopia always includes B vitamins and methylation support in our formulas.

References:

1. Anastasia. Methylation; why is it important for mental health? Food for the Brain. Published March 29, 2021. Accessed March 29, 2023. https://foodforthebrain.org/methylation-why-is-it-important-for-mental-health/
2. NCI dictionary of Cancer Terms. National Cancer Institute. Published February 2, 2011. Accessed March 29, 2023.
   https://www.cancer.gov/publications/dictionaries/cancer-terms/def/methylation[/custom-reference]
3. Steluti J, Palchetti CZ, Miranda AM, Fisberg RM, Marchioni DM. DNA methylation and one-carbon metabolism related nutrients and polymorphisms: analysis after mandatory flour fortification with folic acid. Br J Nutr. 2020;123(1):23-29. doi:10.1017/S0007114519002526
4. Creative proteomics blog. Creative-proteomics.com. Accessed March 29, 2023. https://www.creative-proteomics.com/blog/index.php/brief-introduction-of-one-carbon-metabolism/
5. Purves D, Augustine GJ, Fitzpatrick D, et al. Neurotransmitters. Sinauer Associates; 2001.
6. Salameh Y, Bejaoui Y, El Hajj N. DNA methylation biomarkers in aging and age-related diseases. Front Genet. 2020;11:171. doi:10.3389/fgene.2020.00171
7. Mandaviya PR, Stolk L, Heil SG. Homocysteine and DNA methylation: a review of animal and human literature. Mol Genet Metab. 2014;113(4):243-252. doi:10.1016/j.ymgme.2014.10.006
8. Methylation and homocysteine: A brief overview. Food for the Brain. Published April 21, 2020. Accessed March 29, 2023. https://foodforthebrain.org/nutrition-for-healthcare-professionals/methylation-and-homocysteine/
9. Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36(1):211-239. doi:10.1146/annurev-nutr-071715-050947
10. Shorter KR, Felder MR, Vrana PB. Consequences of dietary methyl donor supplements: Is more always better? Prog Biophys Mol Biol. 2015;118(1-2):14-20. doi:10.1016/j.pbiomolbio.2015.03.007
11. Leech J, Dietitian (MSc Nutrition, Dietetics). MTHFR C677T and A1298C: Explained in plain English. Diet vs Disease. Published March 6, 2016. Accessed March 29, 2023. https://www.dietvsdisease.org/mthfr-c677t-a1298c-mutation/
12. Castiglia P, Sanna V, Azara A, et al. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study. Int J Med Sci. 2019;16(8):1089-1095. doi:10.7150/ijms.32162
13. Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10. doi:10.1016/j.ejmg.2014.10.004
14. Tafuri L, J Servy E, J R Menezo Y. The hazards of excessive folic acid intake in MTHFR gene mutation carriers: An obstetric and gynecological perspective. Clin Obstet Gynecol Reprod Med. 2018;4(2). doi:10.15761/cogrm.1000215
15. Living with MTHFR – S-adenosyl-methionine (SAMe). Livingwithmthfr.org. Accessed March 29, 2023. https://www.livingwithmthfr.org/genetic-education/amino-acids/s-adenosyl-methionine-same
16. Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. 2013;5(9):3481-3495. doi:10.3390/nu5093481
17. Allison J, Kaliszewska A, Uceda S, Reiriz M, Arias N. Targeting DNA methylation in the adult brain through diet. Nutrients. 2021;13(11):3979. doi:10.3390/nu13113979
18. Korsmo HW, Dave B, Trasino S, et al. Maternal choline supplementation and high-fat feeding interact to influence DNA methylation in offspring in a time-specific manner. Front Nutr. 2022;9:841787. doi:10.3389/fnut.2022.841787
19. Riboflavin. Linus Pauling Institute. Published April 22, 2014. Accessed March 29, 2023. https://lpi.oregonstate.edu/mic/vitamins/riboflavin
20. Hustad S, Schneede J, Ueland PM. Riboflavin and Methylenetetrahydrofolate Reductase. Landes Bioscience; 2013.
21. Living with MTHFR – creatine (CK, CPK). Livingwithmthfr.org. Accessed March 29, 2023. https://www.livingwithmthfr.org/genetic-education/amino-acids/creatine-ck-cpk
22. Did you know? Creatine. Com.au. Accessed March 29, 2023. https://mthfrsupport.com.au/2018/11/did-you-know-creatine/
23. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166-173. doi:10.1016/j.exger.2018.04.013
24. Roschel H, Gualano B, Ostojic SM, Rawson ES. Creatine supplementation and brain health. Nutrients. 2021;13(2):586. doi:10.3390/nu13020586

What Is 5-Htp, And Where Does It Come From?

L-5-hydroxytryptophan, or 5-HTP, comes from tryptophan which is an essential amino acid. Tryptophan hydroxylase is the enzyme that converts tryptophan to 5-HTP by adding a water molecule. 

Furthermore, the process of decarboxylation yields serotonin, a neurotransmitter that’s crucial for cognition, learning, sleep, and mood. The conversion of serotonin to melatonin plays a huge role in the regulation of the sleep-wake cycle. 

Serotonin outside the brain can’t cross the Blood-Brain Barrier (BBB). However, tryptophan and 5-HTP can cross the BBB. 

There are many natural 5-HTP sources. Plants are a great source, such as the seeds of African Griffonia simplicifolia. Other rich sources of 5-HTP include intertidal sponges and mushrooms. 

Interestingly, the bacteria Chromobacterium violaceum also naturally performs tryptophan hydroxylation. Its bacterial tryptophan hydroxylase has certain characteristics of the mammalian one.

Health Benefits of 5-HTP

Sleep

5-HTP is a melatonin precursor. Melatonin is a hormone from the pineal gland that regulates the day-night and sleep-wake cycle. Thus, 5-HTP has beneficial effects on sleep. 

In one study, 8 healthy, young adults received either a placebo pill or a 200 mg 5-HTP pill for 17 nights. Their rapid eye movement (REM) sleep increased by 53% compared to placebo baseline.

Another study on 20 older adults with poor sleep quality investigated the effects of 5-HTP on sleep quality. Participants either received 100 mg of 5-HTP every day for 12 weeks, or did not receive anything. The 5-HTP group fell asleep faster after 8 weeks of the supplementation, while the control group still reported the same poor sleep quality.

In animal models, when 5-HTP and GABA were administered together, they significantly improved sleep quality and regulated sleep duration more than either 5-HTP or GABA alone.

Mood And Mental Health

5-HTP is a serotonin precursor. Serotonin plays a major role in mood and cognition.

Inhibiting tryptophan hydroxylase and tryptophan reduction in the diet significantly reduces serotonin levels, which correlates with bad mood. However, women experience low mood more frequently than men upon tryptophan reduction. Also, individuals who have a family history of depression experience much more extreme changes in the mood upon tryptophan reduction.

5-HTP may help with mood in some cases. However, it’s important to never mix 5-HTP with other formulas that may increase serotonin without a doctor’s supervision as it can lead to serotonin syndrome, a potentially life-threatening condition.

Furthermore, 5-HTP also promotes calmness and relaxation. A 12-week long study aimed to demonstrate this, with 10 participants receiving an increasing dosage (20 to 300 mg) of 5-HTP, 3 times a day. Participants reported a significant increase in calmness.

Incorporating tryptophan or 5-HTP into the diet can also improve mood, attention, and memory.

Reduces Appetite And Weight Loss

5-HTP also helps with weight loss by reducing appetite. Hypothalamic serotonin (5-HT) has a role in satiety, likely due to 5-HT1B and 5-HT2C receptors. 

A study included 20 overweight individuals who received either a placebo or 900 mg of 5-HTP per day over 12 weeks. The 5-HTP group showed significant weight loss and felt satiated for longer.

Similar results exist in a number of studies – 19 overweight women received either a placebo or 8 mg/kg of 5-HTP daily for 5 weeks. Women in the 5-HTP group had a lower appetite, and also lost on average 1 kilogram (2.2 lbs) more weight compared to the placebo group.

Side Effects Of 5-HTP

Excess supplementation with 5-HTP might lead to some side effects, including:

• Diarrhea and frequent defecation
• Nausea
• Heartburn and acid reflux
• Stomach rumbling
• Stomach fullness and dizziness
• Serotonin syndrome

In one study investigating the relaxing effects of 5-HTP, some side effects occurred in participants. Namely, participants experienced diarrhea and frequent defecation. However, these side effects correlate with the dosage– participants that had these side effects received 225 mg of 5-HTP per day. Participants’ states improved after lowering the dose to 150 mg of 5-HTP per day [R7].

Furthermore, excess 5-HTP and serotonin can cause other gastrointestinal issues like:

• Nausea
• Heartburn
• Rumbling
• Feelings of fullness 
• And dizziness 

The reports of oral 5-HTP side effects in the literature is why we only include 5 mg of 5-HTP in a spray. 

Serotonin syndrome is when you have too much serotonin in your nervous system. Supplements or medications that increase serotonin levels (like 5-HTP) can lead to serotonin syndrome. The symptoms might range from mild to severe. 

Mild symptoms are:

• Diarrhea 
• Fever 
• Sweating 
• Confusion 

More severe symptoms include: 

• Rigidity 
• Seizures
• Very high fever

5-HTP Dosages 

In order to avoid the negative side effects of excess supplementation, 5-HTP dosages should not be too high.

It is best to keep the dose below 200-300 mg, many studies observe a higher risk of side effects at doses higher than 200-300 mg of 5-HTP. 

To improve your sleep quality, you can incorporate 5-HTP in your bedtime routine. The combination of 5-HTP and GABA significantly improves sleep quality. Try Sleep Breakthrough and Dream Optimizer 30 minutes before bedtime. 

Always consult your medical professional before making any changes in your diet and supplement regime, especially if you’re taking medications.

References:

1. Maffei ME. 5-hydroxytryptophan (5-HTP): Natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology. Int J Mol Sci. 2020;22(1):181. doi:10.3390/ijms22010181
2. Wyatt RJ, Zarcone V, Engelman K, Dement WC, Snyder F, Sjoerdsma A. Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroencephalogr Clin Neurophysiol. 1971;30(6):505-509. doi:10.1016/0013-4694(71)90147-7
3. Sutanto C, Heng CW, Gan AX, Wang X, Fam J, Kim JE. The impact of 5-hydroxytryptophan supplementation on sleep quality of older adults in Singapore: A randomized controlled trial. Curr Dev Nutr. 2021;5(5140372):5140372. doi:10.1093/cdn/nzab037_082
4. Hong KB, Park Y, Suh HJ. Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models. Behav Brain Res. 2016;310:36-41. doi:10.1016/j.bbr.2016.04.049
5. Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients. 2016;8(1):56. doi:10.3390/nu8010056
6. Jangid P, Malik P, Singh P, Sharma M, Gulia AKD. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. 2013;6(1):29-34. doi:10.1016/j.ajp.2012.05.011
7. Kahn R, Westenberg HGM. L-5-Hydroxytryptophan in the treatment of anxiety disorders. J Affect Disord. 1985;8(2):197-200. doi:10.1016/0165-0327(85)90046-1
8. Halford JCG, Harrold JA, Lawton CL, Blundell JE. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 2005;6(2):201-213. doi:10.2174/1389450053174550
9. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992;56(5):863-867. doi:10.1093/ajcn/56.5.863
10. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76(2):109-117. doi:10.1007/bf01578751
11. Turner EH, Blackwell AD. 5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin. Med Hypotheses. 2005;65(1):138-144. doi:10.1016/j.mehy.2005.01.026
12. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The serotonin syndrome: From molecular mechanisms to clinical practice. Int J Mol Sci. 2019;20(9):2288. doi:10.3390/ijms20092288

It’s important to note that having a great night’s sleep is critical for the production of multiple neurochemicals.

There are 7 key players in your brain’s chemical makeup.

1. Dopamine: The Molecule Of Drive And Motivation

If you’ve been feeling overwhelmed and burnt out, with zero energy to get through your day, there could be another mischievous, lurking reason as to why that is. 

It all has to do with your neurochemicals. Most notably, dopamine. When your levels of dopamine are rocking and rolling, life is pretty great. This is because dopamine is responsible for your body’s “reward” system that helps you focus. 

So when you’ve got great levels of dopamine, you feel AWESOME as you work step by step towards your goals. It will reinforce behavior and make you feel good, like that giddy feeling you get when you’re looking forward to something exciting. 

This in turn helps you get into GOOD habits, and avoid the low energy or “burn out” feeling. For example, say you know you’ve got to get in a morning run. When you’ve got good dopamine levels, you’ll think about something FUN in that run that will get you moving and grooving and ready to crush your routine. Dopamine even reinforces memories. Having good levels of dopamine is critical to success. 

There are some natural ways to boost your dopamine:

Sunlight: direct sunlight in the eyes boosts dopamine and serotonin.  Another reason to lock in that morning sunlight ritual.

Cold therapy:  exposure to cold has been shown to boost dopamine by 250%.  That’s an incredible gain.

Nootropics: nootropics are brain enhancing supplements that can directly level up your neurochemicals including dopamine.

We created a personalized nootropic company that produces the most powerful nootropic stacks on the market.  We have several formulas that increase dopamine including: Powerful Solution, Apex, Dopa Drops and Zoned In.

2. Acetylcholine: The Molecule Of Focus

On a day-to-day basis, you have to rely on your BRAIN to maximize on all of the necessary steps that will get you to your end goal. This is true whether your goal is to triple your revenue growth, overcome your strongest competitor, etc.

That’s why investing in your brain is one of the most critical things you can do for your career long term. With all of this in mind, it’s important to think about 3 questions:

1. How long does it usually take you to think up new project ideas?
2. How long does it take you to recall information?
3. How long does it take you to learn something new?

Imagine for a moment what your day would look like if you were able to INCREASE your ability to do all of those things at lightning speeds:

• You would be able to come up with creative new project proposals faster, see results faster, and grow your business faster.
• You would be able to boost your memory and attention span to accomplish double the amount you would have been able to before in a day’s work. 
• And you would be able to learn more at faster speeds to reach your goals and rise above the competition.

The key to making this a reality is acetylcholine.  Your thinking, memory, focus, and attention all rely on acetylcholine.

Eggs are the best source of choline which your body converts into acetylcholine.  

Nootopia has several formulas that boost your acetylcholine on demand including Apex, Mental Reboot AM and Nectar X. 

3. Oxytocin: The Bonding Molecule

Oxytocin is one of the most important molecules for great health, especially for women.  Men thrive on testosterone and women thrive with oxytocin.

The best part of oxytocin is IT’S FREE.  You can get a significant boost in oxytocin by simply hugging someone for 22+ seconds. 

Kids and pets are powerful oxytocin generators.  Just playing with them will give you a potent boost in oxytocin which will have a very positive impact on your health and mental perspective.

4. GABA: The Molecule Of Chill

Do you find yourself getting easily irritated by daily frustrations like: 

• Traffic
• Having nowhere to park
• Your coffee getting cold
• Or your phone battery dying? 

Do you feel like your brain is going a mile a minute with jittery nervousness, and you’re unable to get calm for big meetings or social interactions? 

Would you like to tap into a state of mind where you feel groovy, ready to rock and roll, and able to maintain a positive attitude through anything your day throws at you? 

If you answered YES… Odds are you are LOW or DEFICIENT in the neurochemical GABA. GABA is the anti-stress “molecule of chill.” It’s a critical neurochemical not only for keeping stress levels low and “chillaxed” levels high, but it also plays a major role in keeping all of your other neurochemicals BALANCED.

GABA is flexible. You can control your dopamine, serotonin, and acetylcholine levels with GABA to make them each act more effectively, or reduce it to avoid jitters.

In other words, GABA is key for connectedness. When your GABA levels are optimal, everything works in harmony to bring you groovy vibes.

The great news is that if your levels are currently low… you can get GABA flowing in just 2 minutes. 

Nootopia has 2 powerful GABA boosting formulas: Zamner Juice and GABAlicious.

5. Serotonin: The Molecule Of Stability

If you’re low in serotonin, a couple things start to happen…

1. You struggle to get into a good mood, always feeling blue
2. You begin to lack the drive to do things you know you ought to be getting done
3. Your brain becomes foggy 24/7
4. And you no longer take pleasure in things you used to enjoy doing

Low levels of serotonin are linked to depression, anxiety, and poor sleep. All of which keeps these 4 main negative impacts going in a vicious cycle. 

That doesn’t sound like a very good way to enjoy life to the absolute fullest. So if you’ve started to notice some of these same traits in your own daily life…. 

Getting sunlight is a powerful free way to boost your serotonin.

Carbohydrates are another powerful way to increase serotonin.  This is one of the reasons why sugar and carbs can be additive.  

Nootopia blends that can boost your serotonin include Upbeat, Zamner Juice and Nectar X.

6. Noradrenaline: The Molecule Of Initiation

Do you ever realize partway through a conversation that you’re not really “there” with that person? You feel a bit disconnected, or not very present? 

Have you ever found yourself in the midst of a task when you realize you’re not very focused on what you’re actually doing? 

Would you like to increase your wakefulness to boost your presence, reduce distractions, and pump out hard work effortlessly? 

If you answered YES to any of these questions, then there’s a key neurochemical at play: Noradrenaline.

Not to be confused with adrenaline, noradrenaline is responsible for arousal and wakefulness. We’re not talking about sexual arousal, but rather ALERTNESS and presence. 

When your levels of noradrenaline are LOW, you feel:

• A lack of energy
• Inability to concentrate
• Trouble focusing
• And disconnected

All of this adds up to an unproductive day with your task list piling up, and you’ll have trouble communicating and connecting with others and difficulty keeping your projects and deadlines straight.

Not a great way to get to the next level of your career or increase your business growth.

The GOOD news is your noradrenaline levels don’t have to stay that way. You CAN boost your noradrenaline to optimal levels.

It’s a tricky neurochemical however, because TOO much and you’ll feel wired. You’ll burn out fast. You want to find that zone of magic where you’re in the sweet spot without overkill.That’s when you unlock a gentle extension of focused attention that lights up your brain, with the ability to control your focus throughout the day. 

The best two Nootopia formulas for noradrenaline are Nectar X and Zoned In.

7. Adrenaline: The Molecule Of Aggression

When you hear the word “adrenaline” what do you think of? Maybe you think of:

• Stress
• Fear 
• Your heart racing
• Feeling your heartbeat throbbing in your temples
• Or rapid breathing

Yes – Adrenaline is an important neurochemical for keeping us safe in dangerous moments where we need heightened senses or a flood of energy.  But many people don’t know how adrenaline can be used for SUCCESS.  The optimal levels of adrenaline can transfer your performance for athletic endeavors, workouts and other situations that require intensity and aggression.

It’s possible to access adrenaline without tipping over into fear or the physical signs of stress. When you are in control of your adrenaline levels, some pretty incredible things happen:

• You’re able to push through barriers
• You rise to the next level of focus to push your projects forward
• You surge with intensity and drive, key for any physical task…
• And your mental drive gets combined with your physical capacity to DO IT

Listening to aggressive music is one of the best free ways to activate adrenaline.  What type of music is best for adrenaline differs.  For some it’s rock and metal, others its EDM and gangster rap. 

Many people including fighters, soldiers and athletes are able to generate adrenaline on demand.  They’ve learned how to activate it by switching into an aggressive, high-performance state.

Nootopia has created effective stacks that will boost your adrenaline including Power Solution and Zoned In.

Optimal adrenaline levels = More gets DONE. Now, if you’ve been struggling lately to get things done, there’s a 10 minute solution for that. 

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.

References:

1. Daum K. This Is Why You Procrastinate, and Here’s What to Do About It. Inc.com. Published 2019. Accessed February 7, 2023. https://www.inc.com/kevin-daum/this-is-why-you-procrastinate-heres-what-to-do-about-it.html
2. Le Cunff AL. Why we wait: the neuroscience of procrastination. Ness Labs. Published July 26, 2019. Accessed February 7, 2023. https://nesslabs.com/neuroscience-of-procrastination
3. 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/
4. Cherry K. How multitasking affects productivity and brain health. Verywell Mind. Published April 6, 2010. Accessed February 7, 2023. https://www.verywellmind.com/multitasking-2795003
5. Vimalanathan K, Ramesh Babu T. The effect of indoor office environment on the work performance, health and well-being of office workers. J Environ Health Sci Eng. 2014;12(1):113. doi:10.1186/s40201-014-0113-7
6. Gu J, Liu H, Lu H. Can even a small amount of greenery be helpful in reducing stress? A systematic review. Int J Environ Res Public Health. 2022;19(16):9778. doi:10.3390/ijerph19169778
7. Study shows how taking short breaks may help our brains learn new skills. National Institutes of Health (NIH). Published June 8, 2021. Accessed February 7, 2023. https://www.nih.gov/news-events/news-releases/study-shows-how-taking-short-breaks-may-help-our-brains-learn-new-skills
8. The Biology of traumaTM with Dr. Aimie: 08: Can stored trauma in the body cause self-sabotage? With Dr. Arielle Schwartz, part 1 on. Apple Podcasts. Accessed February 7, 2023. https://podcasts.apple.com/us/podcast/can-stored-trauma-in-the-body-cause-self-sabotage-with/id1658593616?i=1000595588519

Speak up!

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)
• Both excitatory and inhibitory like dopamine 

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.

References

1. Patterson J. Verbal Fluency. In: Encyclopedia of Clinical Neuropsychology. Springer New York; 2011:2603-2606.
2. Shao Z, Janse E, Visser K, Meyer AS. What do verbal fluency tasks measure? Predictors of verbal fluency performance in older adults. Front Psychol. 2014;5:772. doi:10.3389/fpsyg.2014.00772
3. Opasso PR, Barreto SDS, Ortiz KZ. Phonemic verbal fluency task in adults with high-level literacy. Einstein (Sao Paulo). 2016;14(3):398-402. doi:10.1590/S1679-45082016AO3629
4. Reverberi C, Cherubini P, Baldinelli S, Luzzi S. Semantic fluency: cognitive basis and diagnostic performance in focal dementias and Alzheimer’s disease. Cortex. 2014;54:150-164. doi:10.1016/j.cortex.2014.02.006
5. Allan JL, McMinn D, Daly M. A bidirectional relationship between executive function and health behavior: Evidence, implications, and future directions. Front Neurosci. 2016;10:386. doi:10.3389/fnins.2016.00386
6. Ghanavati E, Salehinejad MA, Nejati V, Nitsche MA. Differential role of prefrontal, temporal and parietal cortices in verbal and figural fluency: Implications for the supramodal contribution of executive functions. Sci Rep. 2019;9(1):3700. doi:10.1038/s41598-019-40273-7
7. Mueller KD, Koscik RL, LaRue A, et al. Verbal fluency and early memory decline: Results from the Wisconsin Registry for Alzheimer’s Prevention. Arch Clin Neuropsychol. 2015;30(5):448-457. doi:10.1093/arclin/acv030
8. Cooper JR. Neurotransmitters. In: Smelser NJ, Baltes PB, eds. International Encyclopedia of the Social & Behavioral Sciences. Elsevier; 2001:10612-10619.
9. Traynelis SF, Wollmuth LP, McBain CJ, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010;62(3):405-496. doi:10.1124/pr.109.002451
10. Nuss P. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat. 2015;11:165-175. doi:10.2147/NDT.S58841
11. Bartos M, Vida I, Jonas P. Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci. 2007;8(1):45-56. doi:10.1038/nrn2044
12. Sumner P, Edden RAE, Bompas A, Evans CJ, Singh KD. More GABA, less distraction: a neurochemical predictor of motor decision speed. Nat Neurosci. 2010;13(7):825-827. doi:10.1038/nn.2559
13. Piras F, Piras F, Banaj N, et al. Cerebellar GABAergic correlates of cognition-mediated verbal fluency in physiology and schizophrenia. Acta Psychiatr Scand. 2019;139(6):582-594. doi:10.1111/acps.13027
14. Porges EC, Woods AJ, Edden RAE, et al. Frontal gamma-aminobutyric acid concentrations are associated with cognitive performance in older adults. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(1):38-44. doi:10.1016/j.bpsc.2016.06.004
15. Wendt PE, Risberg J. Ethanol reduces rCFB activation of left dorsolateral prefrontal cortex during a verbal fluency task. Brain Lang. 2001;77(2):197-215. doi:10.1006/brln.2000.2434
16. Li X, Salami A, Avelar-Pereira B, Bäckman L, Persson J. White-matter integrity and working memory: Links to aging and dopamine-related genes. eNeuro. 2022;9(2). doi:10.1523/ENEURO.0413-21.2022
17. Gierski F, Peretti CS, Ergis AM. Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2007;31(1):262-268. doi:10.1016/j.pnpbp.2006.06.017
18. Pérez MD. Desarrollo de un pan de masa madre rico en GABA y péptidos IECA. Diposit.ub.edu. Accessed February 2, 2023. http://diposit.ub.edu/dspace/bitstream/2445/60791/1/MDP_TESIS.pdf#page=77
19. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-208. doi:10.1002/biof.5520260305
20. Nakamura H, Takishima T, Kometani T, Yokogoshi H. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A. Int J Food Sci Nutr. 2009;60 Suppl 5(sup5):106-113. doi:10.1080/09637480802558508
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Due to the alleged cognitive effects of Celastrus paniculatus, sometimes people call it the “elixir of intelligence” or the “elixir of life” in traditional Ayurvedic medicine. Evidence suggests that this plant, especially its oil, improves mental performance and memory, affects neurotransmitters, and helps with pain and inflammation. 

Disclaimer: Most Celastrus studies so far are animal studies. However, we’ve found it an effective nootropic herb, especially with our proprietary extraction technologies.

What Is Celastrus Paniculatus?

Celastrus paniculatus is a tall, woody climber (sometimes known as a climbing shrub) of the Celastraceae family with yellow, corky bark . It grows throughout India and may reach heights of about 2000 meters. The plants have a variety of medicinal properties, including usage for:

• Cognitive impairment
• Sleep
• Joint discomfort
• And post-meal stomach discomfort

The most often utilized plant portion is oil from the seeds (known as Jyothismati oil, JO), which contains different levels of the alkaloids celastrine and paniculatin. Jyothismati has a bitter flavor and a scorching potency. However, the seeds and seed oil are highly therapeutic. The seed oil is beneficial for massage, particularly in vata disorders such as back discomfort, facial muscle weakness, and joint issues .

Note: We’re sharing this list of conditions based on Ayurvedic literature for educational purposes only. Our products contain specific extracts of Celastrus that are not intended to treat any diseases.

What Is SuperCelastrus^TM?

SuperCelastrus^TM are our set of proprietary extracts of Celastrus peniculatus, using a combination of:

• Sonic and ultrasonic extraction
• Lipid suspension and micronization technologies
• Combining various parts of the seed and the plant at various stages of processing

Our extraction technologies allow us to create SuperCelastrus blends that target dopamine, acetylcholine, serotonin, and GABA. 

Health And Brain Benefits Of Celastrus Paniculatus

Celastrus’ Effects on Neurotransmitters 

Clinical studies indicate that Celastrus paniculatus has two main effects on neurotransmitters: 

1. Balancing their levels 
2. Antioxidant and neuroprotective effect

Celastrus paniculatus increases cognitive performance by acting on the acetylcholine level in the brain. It primarily balances neurotransmitters such as serotonin, epinephrine, and dopamine to optimize memory and learning in the brain. 

Celastrus paniculatus also enhances mental wellbeing and promotes a healthy stress response due to its interaction with dopamine, serotonin and GABA receptors. It increases the levels of serotonin, dopamine and noradrenaline by blocking the activity of MAO-A. MAO-A is the enzyme that breaks these neurotransmitters down.

In rats, Celastrus may lower both levels and turnover of noradrenaline, dopamine, and serotonin levels in the brain. According to the researchers, these effects may aid learning and memory enhancement .

Increases Acetylcholine Levels

C. paniculatus seed extract inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine. Blocking this enzyme boosts acetylcholine levels in the brain, improving many aspects of cognitive function .

Taking Celastrus oil for prolonged periods of time can lead to increased cognitive performance and improvements in memory retention. This is due to the fact that Celastrus paniculatus increases levels of acetylcholine in the brain.

Improves Mental Performance And Memory During Stressful Situations

Chronic stress can accelerate aging and neurodegeneration . Stress can also impair some aspects of brain function .

Long-term stress can interfere with working memory, learning, and relaxation responses. According to some experts, Celastrus may help protect the brain from the detrimental effects of stress. Stressed rats that were administered Celastrus oil performed better on learning and memory tests . Another rat study discovered that Celastrus seed oil might boost mental function and memory . 

Improves Myelination

Celastrus paniculatus oil increases the concentration of proteins and phospholipids in the brain leading to the belief that it possibly increases myelination around neurons.

Protects Neurons From Glutamate Toxicity

Glutamate is a chemical that can cause neuronal cell death, Celastrus paniculatus protects the brain from glutamate induced toxicity by blocking NMDA receptors.  

Counteracts And Protects Neurons From Oxidative Stress

Furthermore, the antioxidants in Celastrus paniculatus reduce brain levels of the oxidative stress marker malondialdehyde. Some of its components scavenge hydrogen peroxide and superoxides inside the cells. Aside from counteracting the harmful effects of oxidative stress, it also simultaneously increases glutathione and catalase levels significantly .

Inflammation-Balancing

Studies on Celastrus paniculatus indicate possible anti-inflammatory effects. In addition, there is some indication that Celastrus extract components (sesquiterpene esters) may inhibit inflammatory chemicals such as NF-kB, nitric oxide, IL-6, and TNF-a .

In mice, Celastrus extract had inflammation-balancing effects. In addition, Celastrus seed extract may also ease swelling and discomfort in animal studies .

We need additional clinical studies to confirm this benefit of Celastrus.

Dosage 

Traditional doses of Celastrus paniculatus begin with 10 seeds consumed all at once. If no adverse effects occur, raise the amount to 15, then 20, and eventually 30 seeds.

Due to a lack of clinical study, a safe and effective dosage of Celastrus is unknown. However, Celastrus supplements may contain 400-500 mg of Celastrus paniculatus powder with standard doses of 1 to 2 capsules per day.

Much more study is required to find the best dosage of Celastrus paniculatus.

Side Effects 

Due to a lack of clinical studies, no side effects have been determined for the usage of Celastrus paniculatus.

Celastrus has non-existent toxicity in our lab, as we’ve found its LD-50 to be very high. It also doesn’t cause tolerance over time, so chronic use wouldn’t be a concern.

Celastrus paniculatus FAQ

Is Celastrus Toxic?

There is a lack of clinical studies investigating the health effects and safety of Celastrus paniculatus. However, animal studies have touched upon this topic.

1. Sperm cell depletion and arrest of spermatogenesis was seen when rats received 0.2 ml of the extract in 0.2 ml of peanut oil every 48 hours for 30 days. Furthermore, liver lesions and focal necrosis occurred during the treatment but healed when celastrus supplementation was discontinued.
2. Female albino mice received 300, 2000, or 5000 mg/kg of celastrus seed oil for 42 days. There were no signs of side effects (diarrhea, skin changes, tremors, coma, etc.), toxicity, or lethality caused by the mentioned doses.
3. In our lab, SuperCelastrus, our proprietary extract of celastrus, has shown no toxicity due to very high LD-50. 

Thus, Celastrus paniculatus seems safe to use. However, dosages in animal studies tend to be very high compared to doses humans take, and some health effects don’t carry over. Therefore, clinical evidence in humans is necessary. 

What Are the Effects of Celastrus paniculatus Seed Oil?

Celastrus seed oil shows various nootropic activities in mice and rats. 

1. It inhibits acetylcholinesterase to increase acetylcholine and increase acetylcholine between neurons, thereby boosting memory performance.
2. Celastrus compounds associate with central muscarinic receptors to enhance spatial memory in rats. 
3. The seed oil also interacts with monoamine oxidase A to decrease its activity in mice, and induce mood-boosting effects. 
4. The seed oil supports healthy stress response in mobility-restricted rats.
5. While the chloroform extract showed strong antioxidant properties, the aqueous extract had highest inflammation-balancing activity.  
6. The seed oil supports gastrointestinal health and protects the stomach lining in rats.
7. Methanolic seed extract also supports healthy cholesterol levels.

Keep in mind that while rodent studies led to many scientific discoveries, you are not a rodent. So, we need more clinical studies to confirm these benefits in humans.

What Is the Common Name for Celastrus paniculatus?

Here are some of the common names for Celastrus paniculatus:

• “Black oil plant” because the seed oil is a very dark color
• “Intellect tree” 
• “Climbing staff plant” due to its climbing abilities which result in the plant reaching up to 10-18 m (32-59 feet) tall and having 25 cm (9.8 inches) wide stems
• “The tree of life” in Indian culture, where it’s called “malkankani”. 
• “Jyotishmati” is another name for celastrus in the Sanskrit language (coming from intellect – medha, and memory – smruti), which is often used to refer to the Celastrus paniculatus seed oil.

What’s in the Celastrus paniculatus Leaves?

Celastrus leaves are alternate, broad, and oval/elliptical, and have dentate margins. Compounds found in the leaf extract include steroids, terpenoids, alkaloids, saponins, carbohydrates, and phenolic compounds. Celastrus paniculatus leaves obtained from the forest areas of India also contain fixed oils (in all extract types), flavonoids (in the water extract), and triterpenoids (in water and ethanolic extract). An in vitro study of leaf ethanolic extract reported a total phenolic content of 125.6 mg/gm equivalent to gallic acid in 1 mg/ml of the leaf extract. 

Furthermore, the methanolic extract of celastrus leaves inhibited the growth of Phytophthora capsici fungi, with inhibition being 100%. Celapanin, a sesquiterpene isolated from the ethanolic extract of celastrus, significantly inhibited the growth of S. aureus, and moderately of K. pneumoniae and P. aeruginosa.

Why Is Celastrus paniculatus Called the Intellect Plant?

You might wonder how celastrus got one of its common names – “the intellect plant”. “Jyotishmati” is another name for celastrus in the Sanskrit language. It comes from the words medha, which means intellect, and smruti, which means memory. This is because Celastrus paniculatus was used to improve intellect in traditional Ayurveda medicine. This plant was mentioned in the writings of Charaka, Vagbhata, and Sushruta as a mental health and intellect-boosting agent, with a special focus on the celastrus oil. The ancient prescriptions included celastrus oil mixed with cow’s ghee. It is because of the ancient Indian use of this plant that it became known as “the intellect plant’’.

Bottom Line

Celastrus paniculatus has various medical and therapeutic benefits, such as improving mental performance and memory, exerting certain effects on neurotransmitters, and potentially inflammation-balancing. Although most of these findings come from animal studies, Celastrus is a very popular herb in Ayurvedic medicine with a long history of safe use.

References

1. Lekha G, Mohan K, Samy IA. Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice. Pharmacognosy Res. 2010;2(3):169-174. doi:10.4103/0974-8490.65512
2. Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain. J Ethnopharmacol. 2004;93(2-3):213-219. doi:10.1016/j.jep.2004.03.051
3. Valecha R, Dhingra D. Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice. Basic and clinical neuroscienc. 2016;7(1):49-56.
4. Nalini K, Karanth KS, Rao A, Aroor AR. Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats. J Ethnopharmacol. 1995;47(2):101-108. doi:10.1016/0378-8741(95)01264-e
5. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic activity of Celastrus paniculatus seed. Pharm Biol. 2010;48(3):324-327. doi:10.3109/13880200903127391
6. Olivier B, Zethof T, Pattij T, et al. Stress-induced hyperthermia and anxiety: pharmacological validation. Eur J Pharmacol. 2003;463(1-3):117-132. doi:10.1016/s0014-2999(03)01326-8
7. Ramkumar K, Srikumar BN, Shankaranarayana Rao BS, Raju TR. Self-stimulation rewarding experience restores stress-induced CA3 dendritic atrophy, spatial memory deficits and alterations in the levels of neurotransmitters in the hippocampus. Neurochem Res. 2008;33(9):1651-1662. doi:10.1007/s11064-007-9511-x
8. Kleen JK, Sitomer MT, Killeen PR, Conrad CD. Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore. Behav Neurosci. 2006;120(4):842-851. doi:10.1037/0735-7044.120.4.842
9. Bhagya V, Christofer T, Shankaranarayana Rao BS. Neuroprotective effect of Celastrus paniculatus on chronic stress-induced cognitive impairment. Indian J Pharmacol. 2016;48(6):687-693. doi:10.4103/0253-7613.194853
10. Gattu M, Boss KL, Terry AV Jr, Buccafusco JJ. Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus. Pharmacol Biochem Behav. 1997;57(4):793-799. doi:10.1016/s0091-3057(96)00391-7
11. Jin HZ, Hwang BY, Kim HS, Lee JH, Kim YH, Lee JJ. Antiinflammatory constituents of Celastrus orbiculatus inhibit the NF-kappaB activation and NO production. J Nat Prod. 2002;65(1):89-91. doi:10.1021/np010428r
12. Kothavade P, Bulani V, Nagmoti D, Juvekar A. 100. Cytokine. 2014;70(1):51-52. doi:10.1016/j.cyto.2014.07.107
13. Ahmad F, Khan RA, Rasheed S. Preliminary screening of methanolic extracts of Celastrus paniculatus and Tecomella undulata for analgesic and anti-inflammatory activities. J Ethnopharmacol. 1994;42(3):193-198. doi:10.1016/0378-8741(94)90085-x
14. Rajkumar R, Kumar EP, Sudha S, Suresh B. Evaluation of anxiolytic potential of Celastrus oil in rat models of behaviour. Fitoterapia. 2007;78(2):120-124. doi:10.1016/j.fitote.2006.09.028
15. Kothavade PS, Bulani VD, Deshpande PS, Chowdhury AS, Juvekar AR. The petroleum ether fraction of Celastrus paniculatus Willd. seeds demonstrates anti-arthritic effect in adjuvant-induced arthritis in rats. J Tradit Chin Med Sci. 2015;2(3):183-193. doi:10.1016/j.jtcms.2016.02.004
16. Bidwai PP, Wangoo D, Bhullar N. Antispermatogenic action of Celastrus paniculatus seed extract in the rat with reversible changes in the liver. J Ethnopharmacol. 1990;28(3):293-303. doi:10.1016/0378-8741(90)90080-d
17. Mishra B, John E, Joy K, Badmanaban, Aleesha. TOXICITY PROFILE OF CELASTRUS PANICULATUS SEEDS: A PRECLINICAL STUDY. Asian J Pharm Clin Res. Published online 2020:115-118. doi:10.22159/ajpcr.2020.v13i7.37803
18. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic activity ofCelastrus paniculatusseed. Pharm Biol. 2010;48(3):324-327. doi:10.3109/13880200903127391
19. Gattu M, Boss KL, Terry AV Jr, Buccafusco JJ. Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus. Pharmacol Biochem Behav. 1997;57(4):793-799. doi:10.1016/s0091-3057(96)00391-7
20. Valecha R, Dhingra D. Behavioral and biochemical evidences for antidepressant-like activity of Celastrus paniculatus seed oil in mice. Basic Clin Neurosci. 2016;7(1):49-56.
21. Lekha G, Mohan K, Samy IA. Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice. Pharmacognosy Res. 2010;2(3):169-174. doi:10.4103/0974-8490.65512
22. Arora N, Pandey-Rai S. GC–MS analysis of the essential oil of Celastrus paniculatus Willd. seeds and antioxidant, anti-inflammatory study of its various solvent extracts. Ind Crops Prod. 2014;61:345-351. doi:10.1016/j.indcrop.2014.07.025
23. Palle S, Kanakalatha A, Kavitha CN. Gastroprotective and antiulcer effects ofCelastrus paniculatusseed oil against several gastric ulcer models in rats. J Diet Suppl. 2018;15(4):373-385. doi:10.1080/19390211.2017.1349231
24. Patil RH, Prakash K, Maheshwari VL. Hypolipidemic effect of Celastrus paniculatus in experimentally induced hypercholesterolemic wistar rats. Indian J Clin Biochem. 2010;25(4):405-410. doi:10.1007/s12291-010-0050-x
25. Deodhar, K.A. and Shinde, N.W. Celastrus paniculatus: Traditional uses and Ethnobotanical study. Published online 2015. Accessed August 1, 2023. https://www.researchgate.net/publication/281626232_Celastrus_paniculatus_Traditional_uses_and_Ethnobotanical_study
26. Debnath M, Biswas M, Shukla VJ, Nishteswar K. Phytochemical and analytical evaluation of Jyotishmati (Celastrus paniculatus Willd.) leaf extracts. Ayu. 2014;35(1):54-57. doi:10.4103/0974-8520.141929
27. Avinash, D. K. , and Waman, S. N. Phytochemical Constituents of Leaves of Celastrus Paniculatus Wild: Endangered Medicinal Plant. International Journal of Pharmacognosy and Phytochemical Research. 2014;6(4):792-794.
28. Sharma GN, Kaur H, Shrivastava B, Arora SC. A review from historical to current-Celastrus paniculatus. Int J Pharm Pharm Sci. Published online 2020:15-20. doi:10.22159/ijpps.2020v12i8.38470
29. Harish BG, Krishna V, Sharath R, et al. Antibacterial Activity of Celapanin, a Sesquiterpene Isolated from the Leaves of Celastrus paniculatus Willd. Globalsciencebooks.info. Accessed August 1, 2023.
30. Saini K, Chaudhary A, Sharma RK. Effect of Celastrus paniculatus on trace elements of cerebellum in ageing albino rats. Ann Neurosci. 2012;19(1):21-24. doi:10.5214/ans.0972.7531.180405
    
    

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):

1. D-galactose for 60 days (100 mg/kg body weight)
2. D-galactose and glycine for 60 days (1 g/kg body weight in 0.9% saline solution)
3. Glycine for 60 days 
4. 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.

BiOptimizers Sleep Breakthrough contains glycine powder to support the best sleep. 

Collagen Supplements

Glycine is the building block of collagen. Thus, using collagen supplements like Collagenius might also boost your glycine levels.

References:

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16. Ullah R, Jo MH, Riaz M, et al. Glycine, the smallest amino acid, confers neuroprotection against D-galactose-induced neurodegeneration and memory impairment by regulating c-Jun N-terminal kinase in the mouse brain. J Neuroinflammation. 2020;17(1):303. doi:10.1186/s12974-020-01989-w
17. Ito S. GABA and glycine in the developing brain. J Physiol Sci. 2016;66(5):375-379. doi:10.1007/s12576-016-0442-7
18. Schmidt RW, Thompson ML. Glycinergic signaling in the human nervous system: An overview of therapeutic drug targets and clinical effects. Ment Health Clin. 2016;6(6):266-276. doi:10.9740/mhc.2016.11.266
19. Alves A, Bassot A, Bulteau AL, Pirola L, Morio B. Glycine metabolism and its alterations in obesity and metabolic diseases. Nutrients. 2019;11(6):1356. doi:10.3390/nu11061356
20. Yan BX, Sun YQ. Glycine residues provide flexibility for enzyme active sites. J Biol Chem. 1997;272(6):3190-3194. doi:10.1074/jbc.272.6.3190
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31. McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary Glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection. Ochsner J. 2018;18(1):81-87. Accessed December 2, 2022. https://pubmed.ncbi.nlm.nih.gov/29559876/
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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 dopamine balances 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:

1. Clonidine/caffeine 
2. Clonidine/placebo 
3. Placebo/caffeine 
4. 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. 

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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. 

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