Author: Mr. Noots

Having spent over $150,000 optimizing my brain over the past few decades, the following are powermoves I still follow and recommend. These 12 power moves will help you get the most out of your Nootopia stacks.

Everyone’s brain chemistry is unique. But here are a few universal brain-boosting principles that apply to everyone. These nootropics are not your basic vitamins or supplements. They are very powerful physiological and neurological enhancers.

1. Take The Time To Experiment And Find Your Personal Sweet Spot: More Is NOT Better… OPTIMAL IS MORE

If you’re hardcore, like Matt, you might be tempted to go all in and take as many brain enhancers as possible. However, that can be a big mistake.

One of the core principles of Biological Optimization is to find the ideal dose of each building block and bioregulator for peak performance. This means that optimum brain performance isn’t achieved by taking as many brain enhancers as possible. The goal is to get you to your ideal brain state, stay there, and avoid going beyond. 

Approach brain optimization like a symphony. You want to have the full orchestra playing at the right volumes. You don’t want the cello or drums to “overpower” the rest of the orchestra. You don’t want to just hear “bass” in the mix. 

So, you want to experiment to identify your optimal “brain stimulation sweet spot.” 

That’s where the “Apex Performance” is… AKA: The Zamner Zone.

Too many cognitive enhancers can cause jitters, brain fog, a numbing of your senses, maybe a slight headache, and a dumbing down of your performance. However, when you take too little, you don’t activate the peak performance state you want. 

Especially in the case of Nectar X and Power Solution, it means sipping instead of chugging. See how your brain reacts to ¼ of the tube. Wait for the effect, then manage the dose as you learn how your mind responds to each Breakthrough Brain Stack. 

This means following the 30-day Guided Nootopia Journey, designed to ramp you up into the stacks slowly. This way, you can easily see what works for you and what doesn’t. You can learn the right amount of nootropics that works for you – “What’s too much?” “What’s not enough?” and “What activates YOUR ZAMNER ZONE?” 

Everyone is unique. Neurotransmitter dominance and deficiencies, hormones, and ability to break down each nootropic vary wildly per individual. Your response to Nootopia stacks changes based on your unique genetics, lifestyle, age, food intake, and other factors.

Be patient and just follow the 30-day Guided Nootopia Journey and take notes. This will lead to major improvements in managing your performance and mental state.

2. Reduce Your Caffeine Intake As Nootropics Can Greatly Potentiate Its Effects

This means that 1 cup of coffee will perform like 3-5 cups. We don’t use a lot of caffeine in our blends (unless you want us to because there are more effective ways to optimize your brain and energy). One of the issues you may encounter is feeling anxious drinking the same amount of caffeine you used to. This is especially true with Power Solution, Focused Savagery, and Nectar X. 

Because of your individual genetics, this varies greatly. For example, some people are slow caffeine metabolizers, and ½ a cup of coffee keeps them awake at night. Others can pound a double espresso and take a nap. 

This is why we suggest using decaf or half-caf/half-decaf coffee when you start the nootropics. If you’re super caffeine sensitive, start with decaf. 

Using the modified version of buttered coffee below can take your experience to new heights. THE MAIN POINT IS: YOU MUST FIND YOUR OWN “SWEET SPOT” WHEN IT COMES TO CAFFEINE CONSUMPTION, and this “sweet spot” is going to be very different than it used to be when using these Breakthrough Brain Stacks. 

Note: Just as our nootropic stacks improve cognitive performance, some of these stacks also support and improve adrenal response. Critical to managing how you handle stimulants (like coffee and energy drinks). It’s entirely possible to reverse adrenal damage you may have experienced from excess stress, poor diet, and even genetic issues.

All of that changes today – you are taking control of your mind and body with the most effective brain and body stacks ever assembled. 

3. Use Glucose As A Performance Enhancer 

Nootropics eat glucose for breakfast, lunch, and dinner: The brain is primarily made of DHA (DocosaHexaenoic Acid, an omega-3 fatty acid), but glucose fuels the brain. It CAN run on ketones; however, key areas of thinking are still dependent upon glucose to function. 

If you find yourself “nooted up” but you’re struggling to find the right words and phrases, it’s likely because your high-performance, nootropics-enhanced brain is starving for glucose. 

You don’t need a lot of carbs to optimize this. You just need 10-20 grams: A handful of grapes, a glucose shot, honey-laced tea, or a long-burn carbohydrate like steel-cut oats dusted with cinnamon. 

You can bump up your glucose a bit more when you’re in a high-performance event (all-day meeting, big pitch, playing a championship Chess match, hardcore brain training). The key with glucose is to STREAM IT IN by sipping a beverage or eating slower digesting, complex carbs (rice, oatmeal, etc.). 

4. Minimize Or Avoid Weed, Alcohol, And Medication

Nootropic stacks are “blunted” by bong hits (THC specifically), excess levels of alcohol, and many meds. If you’re committed to getting high and drunk, just use Mental Reboot at night to help you recover and be ready for the next day. 

Mental Reboot is specifically formulated to help remove the detritus (or residue) accumulated in the brain from those drugs and meds. 

Take the night-time oral capsule and daytime sublingual, and you’ll eliminate most, if not all of those toxic residues. 

5. Avoid Protein 

Avoid protein? WOAH! Blasphemy! Yes, protein is the seed of life, but it blunts a lot of nootropic absorption. It can compete with the more fragile nature of nootropics. Therefore, taking your Nootopia stacks “away from” protein is how you’ll best experience the nootropic benefits. Don’t worry, you don’t need to avoid protein throughout the day. 

We suggest taking your Nootropics 60 minutes before or 45+ minutes after a high-protein meal to help you maximize your nootropic absorption.

6. Stack Your Fats 

Many nootropics are fat-soluble. They look for a source of fat to bond to, which helps the nootropic cross through the blood-brain barrier (BBB). 

Stacking all your fats with fat-soluble supplements creates a major breakthrough in nutrient absorption. For example, research has shown you can boost CBD absorption in the bloodstream by 800% when taken with a high-fat meal. You can get similar absorption gains with many other key fat-soluble nutrients. 

Matt has recently increased his vitamin D levels up to 148 ng/ml (top of the range is 100) using this approach while taking half of the vitamin D he was previously consuming. 

We suggest taking all your fats + fat-soluble Nootropics + fat-soluble supplements in one shot. 

This includes: 

1. Nootopia caps: Brain Flow, Upbeat, Focused Savagery, and Apex 
2. Fish oil/Krill oil 
3. Algae oil 
4. Buttered coffee: MCT/butter 
5. Vitamin: A, D, K, and E 
6. CBD/CBG/CBN 
7. Other high-quality fats: olive oil, macadamia nut 

There will be a powerful synergistic effect taking the entire “fat stack” together. It will improve the uptake of your nootropics and moderate the uptake into the brain, which improves long-term performance. So instead of a quick spike in performance, you get a long-term, controlled performance improvement. 

We suggest doing blood tests every three months when making big shifts so you can track the changes in biomarkers. 

Optimize Your Vitamins And Minerals

Many folks are vitamin and mineral deficient. As a result, they’re running on fumes and taking nootropics as a way to recover their performance deficit. 

It doesn’t work like that. We DO ensure each nootropic stack is a complete B-vitamin matrix, but you may be depleted. By ensuring you keep optimal nutrient levels, you will experience better brain performance.

Instead of starting from a minus five (-5) performance level, you’re starting from a plus two (+2) or a plus five (+5). That makes a huge difference in your brain performance improvement scale. Add the right stack on top of an already optimized body, and you’ll be activating a plus ten (+10) or better. That is the difference between the average and superhuman performance. 

Adding Primergen-V and Primergen-M to your daily stack can make a big difference, and adding Magnesium Breakthrough makes a massive difference in balancing your nervous system.

7. Sleep Is The World’s Greatest Performance Enhancer 

Most people are running a sleep deficit. This causes their neurochemistry to malfunction since most natural neurochemicals are produced during sleep. The consequences of inadequate sleep and its negative effects on brain performance are well documented.

This also means your brain isn’t as “clean” as it needs for optimum performance. Your nootropics have to fight beta-amyloid proteins and similar detritus to perform their magic. So getting good sleep is critical to performance. You cannot out-supplement insufficient or poor quality sleep. 

Sleep is your best friend. Your nootropic performance enhancers will be much more magical with enough high-quality sleep. 

8. Drink Water Like You’re Heading Into Deep High Desert 

When you take Nootopia blends, your need for water increases. Some people need double to triple the amount of water they normally would to keep the body hydrated. Water and brain performance are highly interlinked. Even a 1% drop in dehydration will lead to a drop in brain performance. 

When pushing your brain hard and deep, your body needs more water. Matt has had intense workdays where he drank 8 liters of water. 

Powermove: Mineralize Your Water

Adding ¼ to ½ tsp of high-quality salts (we recommend Himalayan or sea salt) is an inexpensive way to get more minerals into your body. The sodium will help you absorb the water more.

For people on ketogenic diets, we recommend adding ½ tsp of cream of tartar with the salt in 2 liters of water once a day to get the necessary potassium. We also recommend using three droppers a day of Primergen-M to get the required amounts of trace minerals. 

Make sure to be POUNDING water throughout the day. 

9. Add A Music Stack 

Music is an activator of neurochemistry. Most people have never thought of music this way, but it’s true for everyone. Everyone has certain songs or genres of music that make them feel certain emotions and states. 

Want to get hyper-aggressive? Put on some Metallica and Tool, and you’re on your way. Want to feel like you’re on an epic adventure? Put on some soundtrack music. Feel melancholic and want to process those emotions? Put on some sad ballads. Want to feel euphoria? Put on EDM and start dancing (see tip #10). 

The Nootopia blends will synergize with music and amplify those states. This is a powerful tool in the “State Creation Toolbox.”

10. Movement is LIFE 

Many people take supplements and immediately become sedentary. They sit in one place and expect the supplement to do their heavy lifting. That’s not how it works. 

With Nootropics, first, you’re in a race to get the active ingredients (the “stack”) into the bloodstream and then through the Blood-Brain Barrier (BBB). It takes blood flow to make that happen. Passivity is the enemy of blood flow – sitting sucks for optimizing brain performance. 

The ideal would be a 5-15 minute moderate cardio workout: biking, walking, yoga, swimming, etc. 

Pressed for time? Don’t worry because you don’t need to do a full workout to activate the nootropics. Sixty seconds of movement every hour will make a massive difference in your energy and brain performance. 

The key is to make it a habit. Put an alarm or notification on your phone “to move.” Micro bouts of movements are all that’s needed. Here are a few simple Power moves you can do: 

1. A walk around the block 

2. 1 set of 10 air squats (bodyweight squats) 

3. 1 set of push-ups 

4. DANCE! 

5. A few yoga poses 

Whatever you can do to accelerate blood flow will dramatically aid the performance of your nootropic stacks.

In fact, why don’t you stand up right now and do five air squats?

Did you do them yet? C’mon… It’s all about action. LIFE IS MOVEMENT. GO! 

11. Push Your Brain: HARD, FAST, AND DEEP 

To truly experience the power of Nootopia, you must activate your mind and push it. Nootropics don’t “do the work for you”; they’re like steroids (minus the side effects). Even someone on steroids needs to go to the gym to get the benefits. 

Great opportunities to activate your mind and take it to new heights with Nootopia: 

• Long workdays 
• Strategic planning meetings 
• Creative work (songwriting, writing, copywriting, art, etc.) 
• Hyper-competitive video gaming 
• Presentations (sales, interviews, teaching, etc.) 
• Intense brain training 

12. Create The Perfect Day Before It Starts 

When your day starts, we suggest starting with prayer and meditation. Take this quiet time to craft the perfect day in your mind. Here are some questions you can ask to help create it: 

• What’s in your schedule? 
• Which state is ideal for your activities? 
• What do you want your day to feel like? 

First of all, those questions will help you shift into the state you envision. Second, the answer to those questions will help you choose the ideal Nootopia stack based on what state you want to activate.

Glutamate is the most abundant neurotransmitter in your brain. And while it is critical for many aspects of cognitive function and wellbeing, you don’t want to have too much of it because too much can kill neurons. Excess glutamate can also contribute to anxiety, insomnia, brain fog, and other cognitive problems.

Importantly, using too many stimulating nootropics can throw off your brain’s glutamate balance. To optimize your cognitive function, you need to address the root causes of glutamate imbalances and consider balancing out your nootropic protocol. This article will cover those root causes and ways to prevent excess glutamate. 

This article is part of our 3-part glutamate series.

Part 1: What are glutamate neurotransmitters and their important roles?

Part 2: 5 signs of glutamate imbalance

Now, let’s dive in on how you can optimize your brain glutamate levels.

How To Balance Brain Glutamate vs. GABA Levels

Balancing glutamate levels goes hand in hand with balancing GABA (gamma-aminobutyric acid). They are the most abundant neurotransmitters in the brain and work together to balance brain activity.

Excess brain glutamate typically arises from inflammation and danger responses that trigger neuronal deaths. Therefore, aside from directly increasing GABA, you should investigate the root causes of neuroinflammation and leaky blood-brain barrier. If you’re using nootropics, you’ll also need to consider balancing the stimulating ones with calming ones.

Reducing Neuroinflammation

As the name suggests, neuroinflammation is inflammation of the nervous system. It can come from neural injuries, blows to the head, toxins, or infections.

When you have too much inflammation and oxidative stress, your glutamate-releasing neurons and brain immune cells release glutamate. The excess glutamate outside of neurons also triggers more glutamate release, further amplifying the inflammation. 

Unfortunately, the overwhelming amount of glutamate in the brain can also kill neurons. This is a key pathology of poor cognitive function, along with all neurologic and mental health disorders. 

Because glutamate has opposing functions to GABA, GABA  supplements or GABA-boosting supplements may help to an extent. However, these don’t fix neuroinflammation and oxidative stress. 

The first key to balancing glutamate is to address neuroinflammation. Many nootropics also work by managing brain inflammation and oxidative stress. You also want to investigate your neuroinflammation diet and lifestyle root causes. 

Work with a qualified practitioner to investigate and address the following root causes that may contribute to glutamate imbalances:

• Food-related inflammation and oxidative stress such as food allergies, nutrient deficiencies, and lack of dietary antioxidants
• Day to day stress, which may be managed with practices such as yoga and meditation
• Poor sleep quality and any issues that could be keeping you from your best sleep
• Mental health issues and traumas
• Infections or lingering inflammation from infections
• History of brain injuries, concussions, or head injuries
• Toxic exposures that can cause brain inflammation, such as toxic mold exposure

Most herbs and spices have anti-inflammatory properties. Ginger, turmeric, cinnamon, garlic, and rosemary are best for brain health and function. For example, turmeric contains a compound called curcumin, which has antioxidant and anti-inflammatory properties. Green tea also contains powerful antioxidant and anti-inflammatory substances.  

Yoga and meditation, as well as exercising, can reduce neuroinflammation. These physical activities increase stress resilience and reduce stress-induced inflammatory mediators. Therefore, by managing stress, these activities can reduce neuroinflammation.

Eating The Best Diet For Your Brain

The best diet for brain function can be individual depending on your genetic makeup and health status. Some people may have the best brain function and glutamate balance on ketogenic diets. In contrast, others do better on higher-carb Mediterranean-style or even plant-based diets. 

Currently, there is more literature supporting the Mediterranean diet for brain health than other diets. It uses ingredients and foods rich in antioxidants and has anti-inflammatory properties. For example, it is high in omega-3 intake with fish intake, reduces processed carbohydrate intake, and incorporates large amounts of fruit and vegetables.

However, the literature supporting ketogenic diets for brain and neurological health is also growing. Ketosis may help with many neurological disorders by reducing glutamate while increasing GABA and glutamine.

We believe that the best way to find out your healthiest diet is to try the diet and see how it feels. 

Repairing The Leaky Blood-Brain Barrier

The blood-brain barrier (BBB) is a physical barrier that protects the brain while allowing in certain nutrients and other building blocks through. If the barrier is disrupted, certain substances that typically can’t reach the brain will get to it, potentially causing inflammation.

An inflamed brain with compromised blood-brain barrier is called a “leaky brain.” It doesn’t mean that your brain is leaking out. Instead, it means that harmful substances and inflammatory signals can pass through the barrier into your brain, including too much glutamate.

Signs and symptoms of a leaky BBB may include :

• Brain fog 
• Memory loss
• Anxiety, depression, and mood disorders 
• Fatigue 
• Headaches and migraines
• Seizure disorders 

Inflammation in the body can also make your blood-brain barrier leakier. 

Ways to repair your BBB include :

1. Improve Your Gut Bacteria With Probiotics And Synbiotic Supplements 

Studies suggest that the gut microbiota communicates with the central nervous system. Gut bacteria can influence your brain by:

• Reprogramming immune cells 
• Boosting cytokine release
• Generating bacteriophages (viruses that infect bacteria)
• Translocating from the gut into the bloodstream
• Crossing the BBB

Gut bacteria release substances and metabolites into the bloodstream that can easily cross the BBB or interact with barrier cells, affecting the central nervous system. Communication between the gut and the brain can affect cognitive functions and regulate stress-related behaviors. For example, your gut bacteria can make you feel sad and uneasy. 

Therefore, we can repair BBB by improving gut microbiota with certain probiotics.

2. Avoid Gluten And Alcohol 

Food sensitivity can cause inflammation. For example, some people’s immune systems perceive food and dietary proteins as foreign invaders, resulting in gut mucosal barrier inflammation.

A leaky gut can impact other organ systems, causing a BBB to become leaky.

Since a diet rich in gluten and alcohol can lead to a leaky gut, it is no wonder that it can also lead to disrupted BBB. Therefore, if you’re trying to repair your BBB, consider avoiding gluten and alcohol.

3. Consume Food With Omega-3 Fatty Acids, Vitamin B, Magnesium, and Vitamin D

Omega-3 fatty acids help maintain the integrity of the blood-brain barrier, especially in the aging population. These healthy fats inhibit the production of vesicles, or small bags that transfer minerals, vitamins, and even unwanted material across the blood-brain barrier.  

B vitamins are also crucial for the BBB. Vitamin B1 deficiency disrupts the BBB, and supplementation can restore the BBB again. B12, B5, and B9 (folate) vitamins can also help reduce homocysteine and support BBB repair if you have high homocysteine.

Magnesium is also a mineral that exhibits protective benefits on BBB, especially in the presence of inflammation and infections. Multiple experimental models have indicated that magnesium sulfate protects the BBB integrity.

On the other hand, vitamin D is an effective anti-inflammatory and immune-balancing nutrient. Vitamin D receptors may be found in every cell in your body. It prevents leaky brain by lowering inflammation and reducing disruption of the blood-brain barrier. 

4. Use Herbs And Spices That Contain Curcumin 

Curcumin preserves the BBB in rat and mouse models of brain injury from lack of blood flow, most likely because of its anti-inflammatory and antioxidant properties. Curcumin appears to increase enzymes that prevent blood vessel inflammation, so it reduces BBB damage and permeability. 

5. Get Enough Sleep

Sleep and sleep disorders have a negative effect on the blood-brain barrier.  Sleep deprivation disrupts the connections between pericytes, cells that line the capillaries and venules,  and brain endothelial cells. This disruption can lead to a leaky BBB. 

Whereas, by promoting the removal of waste via the BBB, sleep aids in brain biological control. 

6. Try To Reduce Stress 

Stress may impair the blood-brain barrier, which is one of the broad impacts of such stressors on brain function.

7. Manage your homocysteine levels

Homocysteine is a neurotoxic and inflammatory amino acid generated by methionine metabolism.

It can damage neurons leading to cognitive decline, depression, and memory loss in humans. Homocysteine deficit, as well as a lack of folate and vitamin B12, can disrupt certain metabolic pathways, causing calcium influx, abnormal protein buildup, cell death, and neuronal death. 

The negative effect of homocysteine may potentially be mediated via glutamate receptor subtype activation. Folate, glutamate receptor inhibitors, and different antioxidants can all help to inhibit homocysteine’s neurotoxic effects.

By repairing the barrier with certain supplements, such as vitamin B12, B5, and folate, you can improve glutamate balance and stop further damage. 

Balancing Stimulating Nootropics With Calming Ones 

Many nootropic users are, like our co-founders, high performers who always push the envelope on their physiology and cognitive function. Great stimulating nootropics allow you to perform at your maximal level if your brain has the resources for it. 

For these nootropics to continue working, you need to also allow your brain to recover, replenish, and restore. You need to have periods of sympathetic and parasympathetic optimization.

This is why our individualized nootropic programs cycle between intensity and recovery. We take into account your brain’s need for balance so you don’t fatigue your receptors and continue to maximize your cognitive performance. 

Also, our formulations balance excitatory nootropics with inhibitory ones so you don’t experience overstimulation. Stimulating nootropics boost awareness, banish brain fog, and make you more alert during your daily activities. On the other hand, calming nootropics prevent jitters and promote a calm focused flow. They can also help you destress and relax at the end of your day.

Supplements That Increase Glutamate Levels

Many supplements and foods, such as taurine and vitamin C, can help you increase your brain glutamate levels. The following ingredients can increase brain glutamate:

Glutamine

Glutamine is a conditionally essential amino acid. It is normally the most abundant amino acid in the blood. It is an abundant fuel source for certain cells and it is present in many dietary supplements and foods. 

This amino acid plays a role in metabolism and cell functioning. In terms of brain and optimizing brain capacity, it serves as a glutamate precursor. It can also slowly cross the blood-brain barrier. 

Consuming glutamine can increase levels of glutamate via a process called deamidation (a functional group of glutamine is removed or replaced). In this process, the enzyme glutaminase turns glutamine into glutamate. 

L-theanine

L-theanine is a relaxing amino acid found only in green tea. In animals, L-theanine raises serotonin, dopamine, and GABA levels in the brain.

By removing glutamate from the synaptic cleft in the brain, L-theanine can help maintain the correct metabolism of the neurotransmitter glutamate. Furthermore, L-theanine significantly enhances the synthesis of glutamine, which increases levels of glutamate by deamination. 

What’s Next?

Glutamate is a very important neurotransmitter in the brain, but it is important to keep it in balance. Aside from using nootropics, you want to work on reducing neuroinflammation and repairing the blood-brain barrier for the best brain function.

Nootopia personalized nootropic programs take into account individual glutamate imbalance. We also cycle between intensity and recovery so you can prevent excess glutamate and receptor burnouts. Visit us here and choose a product/products that will help you discover the best version of yourself. 

References:

In addition, many natural substances block acetylcholinesterase, an enzyme that breaks down acetylcholine in your synapses. This blockage increases brain acetylcholine. At high doses, these substances act like poisons that can cause paralysis and deaths, but at low doses, they can work as nootropics. 

This article is part 3 of a 3-part series.

Part 1: What is acetylcholine and what are its important roles?

Part 2: 7 Signs you could have low brain acetylcholine levels

Part 3: How to boost your brain acetylcholine levels

Dietary sources of acetylcholine precursors

You can boost acetylcholine production in the brain and the rest of your body by consuming choline-rich food sources such as :

• Egg yolks
• Liver
• Salmon
• Beef
• Cauliflower
• Bacon
• Milk
• Dairy products
• Quinoa
• Amaranth
• Edamame
• Cruciferous vegetables

Nootropic supplements that increase acetylcholine in the brain

Nootropics that increase acetylcholine may work by:

• Inhibiting its breakdown by inhibiting acetylcholinesterase
• Directly stimulating acetylcholine receptors
• Providing the building blocks necessary for the creation and release of acetylcholine in the brain

Aside from being a building block for acetylcholine, choline is also important for heart health, detoxification, and healthy pregnancy.

Below we briefly discuss some of the most common cholinergic compounds used as nootropics nowadays and their function in acetylcholine release.

Alpha-GPC

L-Alpha glycerylphosphorylcholine (Alpha-GPC) is a bioavailable form of choline that crosses the blood-brain barrier. However, Alpha-GPC occurs in small amounts naturally. It is made by deacetylation of phosphatidylcholine from soy or sunflower. 

Choline makes up 40% of Alpha-GPC’s total weight. Inside the brain, it gets converted into phosphatidylcholine and subsequently broken down into choline as needed. Alpha-GPC then provides the necessary choline to make acetylcholine. It showed promising results in optimizing memory and learning. 

Bacopa monnieri

Also familiar as Brahmi and originating from ancient India, this supplement enhances cognition and long-term memory. Bacopa is an adaptogen, which means it promotes a balanced stress response. It also supports the balance of serotonin, dopamine, and acetylcholine in the brain. Also, Bacopa inhibits acetylcholinesterase, increasing synaptic acetylcholine.         

Ginkgo biloba

Ginkgo biloba is one of the most famous and oldest herbs known to improve cognitive function and stamina. Its activities in the brain include:

• Increases acetylcholine levels
• Reduces acetylcholine breakdown 
• Modulating choline uptake and acetylcholine release
• Having antioxidant activities, which protect brain cells from oxidative damage and glutamate toxicity
• Increases blood flow to the brain 
• Increases acetylcholine muscarinic receptor activation and modulates serotonin in a way that affects choline function 

Huperzine A

Huperzine-A is extracted from Chinese moss Huperzia serrata. It is an acetylcholinesterase inhibitor, inhibiting acetylcholine breakdown and increasing acetylcholine in our brain. Consumers report this supplement useful for increasing their mental energy, cognition, and clear thinking.

Vinpocetine

Vinpocetine is a derivative of vincamine, a substance derived from the periwinkle plant. It is a nootropic that increases brain acetylcholine levels and blood flow. Also, it improves alertness, cognition, and memory.

Citicoline

Citicoline or Cytidine Diphosphate Choline (CDP-Choline) is naturally present in every cell in your body. CDP-Choline has 18% choline by weight. It can either cross the blood-brain barrier intact or get digested into cytidine and choline before absorption.

Conclusion:

Acetylcholine is a very important neurotransmitter if you’re looking into nootropics to boost your cognitive function. However, it is important to keep in mind that neurotransmitters work in balance. Also, you need to cycle between the yin and yang of nootropics in order to continue performing optimally. Therefore, your nootropic program should be personalized based on your neurotransmitter profile, goals, and your overall health.

To get your personalized nootropic program, fill out this quiz. 

References

1. Wiedeman AM, Barr SI, Green TJ, Xu Z, Innis SM, Kitts DD. Dietary choline intake: Current state of knowledge across the life cycle. Nutrients. 2018;10(10):1513. doi:10.3390/nu10101513
2. Millard HR, Musani SK, Dibaba DT, et al. Dietary choline and betaine; associations with subclinical markers of cardiovascular disease risk and incidence of CVD, coronary heart disease and stroke: the Jackson Heart Study. Eur J Nutr. 2018;57(1):51-60. doi:10.1007/s00394-016-1296-8
3. Guerrerio AL, Colvin RM, Schwartz AK, et al. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr. 2012;95(4):892-900. doi:10.3945/ajcn.111.020156
4. Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study. FASEB J. 2018;32(4):2172-2180. doi:10.1096/fj.201700692rr
5. Canal N, Franceschi M, Alberoni M, Castiglioni C, De Moliner P, Longoni A. Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. Int J Clin Pharmacol Ther Toxicol. 1991;29(3):103-107. Accessed December 22, 2021. https://pubmed.ncbi.nlm.nih.gov/2071257/
6. Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013;16(4):313-326. doi:10.1089/rej.2013.1431
7. na; EGb 761: Ginkgo biloba extract, Ginkor. Drugs R D. 2003;4(3):188-193. doi:10.2165/00126839-200304030-00009
8. Nathan P. Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology? Med Hypotheses. 2000;55(6):491-493. doi:10.1054/mehy.2000.1099
9. Saxena A, Qian N, Kovach IM, et al. Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases. Protein Sci. 1994;3(10):1770-1778. doi:10.1002/pro.5560031017
10. Medina AE. Vinpocetine as a potent antiinflammatory agent. Proc Natl Acad Sci U S A. 2010;107(22):9921-9922. doi:10.1073/pnas.1005138107
11. National Toxicology Program, U.S. Department of Health and Human Services. Chemical Information Review Document for Vinpocetine [CAS No. 42971-09-5].; 2013. Accessed December 22, 2021. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/vinpocetine091613_508.pdf
12. Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5’-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-145. doi:10.1385/JMN:27:1:137
13. Synoradzki K, Grieb P. Citicoline: A superior form of choline? Nutrients. 2019;11(7):1569. doi:10.3390/nu11071569

Symptoms of acetylcholine deficiency: altering acetylcholine pathway

This article is part 2 of a 3-part series.

Part 1: What is acetylcholine and what are its important roles?

Part 2: 7 Signs you could have low brain acetylcholine levels

Part 3: How to boost your brain acetylcholine levels

Brain fog

Acetylcholine deficiency may cause problems with memory, learning, recall, focus, energy level, etc. Symptoms of brain fog or mental fatigue are classic acetylcholine deficiency symptoms, such as the inability to focus, poor concentration, lack of mental sharpness and clarity, learning and memory troubles, etc. 

Some root causes of brain fog include chronic stress, a lack of sleep, and an unbalanced and unhealthy diet, all of which can reduce acetylcholine in the brain. In most cases, getting rid of brain fog requires addressing the root causes.

Inability to focus and ADHD

Low acetylcholine contributes to key symptoms of ADHD. The most common symptom of ADHD is the inability to focus on a single uninteresting task. Other symptoms may include:

• Forgetting to complete a task
• Being inclinable towards distraction
• Difficulties sitting still
• Interrupting other people while talking

Classic amphetamine medications that treat ADHD work partly by increasing brain acetylcholine. In addition, cholinergic drugs such as galantamine have helped with ADHD symptoms in children and adolescents. 

Forgetfulness, memory problems, and Alzheimer’s disease

Poor cholinergic activity and low levels of acetylcholine in the brain are linked to cognitive decline and memory problems like dementia.

Acetylcholine plays a central role in the development of Alzheimer’s disease. The disease manifests itself as gradual destruction of cholinergic neurons—the neurons that use acetylcholine. Impairment of these neurons makes it more difficult for acetylcholine to transmit neuronal signals, thus affecting memory, recall, and learning.

Neuritic plaques composed of amyloid-beta protein are characteristic of the brain affected by Alzheimer’s disease. They are correlated to the cholinergic markers’ reduction. Moreover, cholinergic deficit is related to amyloid beta accumulation, which causes neuronal loss and impairment. 

Most successful Alzheimer’s drugs inhibit acetylcholinesterase, an enzyme responsible for acetylcholine breakdown. The inhibition may increase acetylcholine levels.

Muscle fatigue

You need acetylcholine in your neuromuscular junctions to contract your muscles. During exercising, acetylcholine levels drop, which is why you get muscle fatigue. Whereas the recovery of both acetylcholine and acetylcholine neurons, which require acetylcholine breakdown, is important for exercise recovery. 

Learning difficulty

Many neurological disorders and neurotransmitter imbalances can cause learning difficulties, such as dyslexia, dyscalculia (struggle with math), dysgraphia (struggle to write), and ADHD. It could be age-related, but can also be partly genetics, developmental, and environmental.  

Given how important acetylcholine is, it makes sense that acetylcholine imbalance contributes to many learning difficulties. However, increasing acetylcholine alone may not be enough to cure these conditions.

Postural orthostatic hypotension and tachycardia syndrome (POTS)

Orthostatic or postural hypotension is abnormally low blood pressure when a person suddenly stands up too quickly after sitting or lying down. Symptoms include: 

• Dizziness
• Lightheadedness
• Rapid increase in heart rate
• Fainting
• Weakness
• Confusion
• Nausea

In most cases, these symptoms could be due to dehydration or long rest and are not dangerous. However, in postural orthostatic tachycardia syndrome (POTS), the autonomic system cannot regulate blood pressure properly, causing you to feel these symptoms.

The cause of neurogenic orthostatic hypotension is a failure of noradrenergic neurotransmission associated with a range of other autonomic disorders. POTS patients often also have symptoms of acetylcholine dysfunction, such as reduced saliva function, slowed gut movement, nausea, constipation, and bladder dysfunction.  An antibody that blocks acetylcholine function can also cause autonomic disorders that lead to POTS.

In a small clinical study involving 15 patients, acetylcholinesterase inhibition helped neurogenic orthostatic hypotension  The drug (pyridostigmine) significantly increased blood pressure, reduced orthostatic heart rate, and improved the overall clinical image of the patients.   Another clinical study of 17 patients confirmed this finding.

Chronic inflammation

Acetylcholine is a key neurotransmitter in the inflammatory reflex. The reflex is how your nervous system responds very quickly to inhibit acute inflammation and prevent the inflammation from causing too much damage.

In the inflammatory reflex, acetylcholine controls inflammation via the vagus nerve. The vagus nerve communicates between the brain and the immune cells. Together, these systems modulate inflammatory responses both through neuronal signals and the blood. 

In the immune system, acetylcholine breakdown at the correct times and places reduces inflammation. 

Therefore, acetylcholine dysregulations tend to go hand-in-hand with chronic inflammation.

Conclusion 2: 

Low acetylcholine may correlate with brain fog, fatigue and mental inclarity, forgetfulness, etc. It may also manifest as chronic inflammation and muscle fatigue. Therefore, you want to learn to maintain healthy acetylcholine levels. In part 3 of this 3-part series, we will cover natural ways to increase acetylcholine levels. 

References

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What is acetylcholine?

This article is part 1 of a 3-part series:
Part 1: What is acetylcholine and what are its important roles?
Part 2: 7 Signs you could have low brain acetylcholine levels
Part 3: How to boost your brain acetylcholine levels

Acetylcholine is one of the first described neurotransmitters with essential roles in memory and cognitive functions. It also works as intracellular messenger molecules outside of the nervous system, covering various brain and bodily functions. As its name suggests, it refers to a complex chemical structure made of acetic acid and choline.

If a body’s tissues use acetylcholine or respond to its stimuli, they are cholinergic. On the other side, substances that antagonize acetylcholine’s action on tissues are called anticholinergics. The proper communication between cholinergic and anticholinergics is vital for the appropriate function of the brain and other organs.

Important roles of acetylcholine for cognitive performance 

Acetylcholine is a ubiquitous chemical in our body and is involved in many cognitive processes, such as:

• Alertness
• Attention and focus 
• Memory
• Mood
• Neuroplasticity
• Long-term potentiation
• Creativity
• Verbal fluency
• Vagus nerve tone
• Motivation
• Awareness
• Learning

Acetylcholine acts as both neurotransmitter and neuromodulator in your brain and spinal cord. As a neuromodulator, it controls the magnitude of transmitted nerve signals between neurons, adjusting neuronal excitability, synaptic plasticity, and nerve signal transmissions. Last but not least, acetylcholine also coordinates the firing of neurons.  

If you have low acetylcholine, you may experience problems with some aspects of cognitive functions that require acetylcholine as mentioned above. Therefore, you want to understand how to keep acetylcholine at optimal levels. But, let’s first briefly review how it affects mental processes.

Alertness

Acetylcholine regulates alertness and the sleep-wake cycle. It interacts with other stimulating neurotransmitters and hormones like dopamine, histamine, and norepinephrine to stimulate wakefulness. Cholinergic activities increase during alertness and waking and decrease during certain sleep stages.

Attention and focus

Acetylcholine is not only important in learning and memory, but also in stimulating attention and alertness. 

In a rat study, putting them in a situation that required focus significantly increased acetylcholine in the brain. Furthermore, making the task more difficult or distracting the rats further increased the acetylcholine levels. The study concluded effort to sustain attention increases brain acetylcholine levels. 

In a clinical study involving 60 healthy females, citicoline supplements, which increased acetylcholine, improved their focus.  

Memory

Higher intakes of acetylcholine precursor or supplements that prevent acetylcholine breakdown may help people facing memory issues. 

Acetylcholine has a long association with memory and cognitive function. Significant loss of acetylcholine in aging, along with the development of dementia, leads to impairments of memory. Acetylcholinesterase inhibitors, which stop acetylcholine breakdown, have shown significant benefits for memory and Alzheimer’s disease severity.

In rats, lifetime supplementation with choline significantly improved their memory and prevented the formation of amyloid-beta plaques, a protein linked to Alzheimer’s disease. 

In a clinical study involving 2,195 elderly men and women, individuals with higher blood choline levels had better learning and memory performance. 

The hippocampus is your brain’s memory center. Whereas, your cerebral cortex is responsible for higher-order brain functions such as sensory, perception, memory, association, thoughts, and reasoning. In monkeys, a disrupted supply of acetylcholine in these two brain regions impaired their memory and ability to acquire new information. These symptoms were similar to human amnesia (memory loss). 

There is a hypothesis that depleting acetylcholine may lead to neurodegenerative diseases like dementia and Alzheimer’s disease. However, it’s still unclear which is the cause or the effect.

Mood

The neurotransmitter serotonin is most commonly associated with depression and other mood disorders. However, there is evidence that other neurotransmitters, including acetylcholine, may also play a role in these conditions. 

Clinical studies suggest excess acetylcholine in some regions of the brain may be a reason for low mood. Therefore, we can conclude the cholinergic system has been significantly linked with mood regulation.

Although its role in depression is not well established, reports show drugs blocking nicotinic acetylcholine receptors have antidepressant effects in rodents. Additionally, the same drugs helped with depression symptoms in humans if used in combination with more traditional antidepressants. 

More studies are required on acetylcholine and mood, as the cause-effect relationship has not been well established yet. More precisely, the fact that high levels of acetylcholine have been linked to depression does not mean that too much acetylcholine causes depression. Also, high levels of acetylcholine most likely are not the only cause of depression, but only a small part of a more complex system. 

Neuroplasticity

Neuroplasticity refers to your nervous system’s ability to change, modify, and adapt in response to stimuli and challenges. These changes could be structural or functional and may happen at any age.

Researchers used to think that the brain only grows and adapts during childhood. However, newer research shows many brain aspects can change, even in adulthood.

On the level of one nerve cell (neuron), there is synaptic plasticity. Synaptic plasticity is the adaptation of synapses (neuronal connections) to store new information and memories. Acetylcholine plays a central role in this process.

Long-term potentiation

Long-term potentiation (LTP) is one of the mechanisms underlying learning and memory. It is how your brain responds to stimuli and adapts according to experience. The more often you use a certain neuronal pathway or cognitive skills, the stronger or more potentiated their synapses become.

In rats, acetylcholine lowered the threshold for long-term potentiation in the hippocampus (the brain’s memory center). Nicotine activates a type of acetylcholine receptor called the nicotinic acetylcholine receptor. In mice, administering nicotine, which activates the nicotinic acetylcholine receptor, induced long-term potentiation. 

Creativity

Although there are no studies directly linking creativity to the levels of acetylcholine in the brain, we may connect the whole story with sleeping. 

During the rapid eye movement (REM) sleep, we experience the activation of various parts of the neocortex. The neocortex is a set of brain layers responsible for higher-order brain functions such as cognition, spatial reasoning, language, etc.   

REM sleep is when acetylcholine floods the brain and disrupts the connection between the neocortex and hippocampus, placing both in a flexible state, enabling neurons to be more easily formed and strengthened. This allows the neocortex to search for similarities between unrelated things and concepts, which may contribute to creativity, memory, and learning.

Many aspects of creativity require holding different thoughts in your memory. Therefore, you need to have a well-functioning brain with healthy levels of acetylcholine to be creative, even though acetylcholine doesn’t work directly in creativity.

Verbal fluency

An observational study on 1,391 subjects searched for a correlation between dietary choline intake, brain morphology, and cognitive function. Results show better visual and verbal memory performance in patients with a higher choline intake. 

Also, a small-scale clinical trial on healthy male subjects tested whether the daily supplementation of 500-1,000 mg of dietary choline improves verbal memory, verbal fluency and working memory. The choline supplement only improved these aspects of cognitive function in subjects whose baseline cognitive performance was below average. This means subjects with average cognitive performance did not benefit from supplementation. Moreover, high-performing subjects had worse cognitive function after supplementation. 

Memory and learning performance significantly decline in neurodegeneration. The cholinergic system is the main target in the clinical manifestation of mild cognitive impairment (MCI) and hippocampal degradation. A clinical study aimed to better understand how the cholinergic system contributes to episodic memory dysfunctions in MCI. The authors examined the functional and structural integrity of the cholinergic system in 20 MCI patients and 20 healthy controls. Neither structural nor functional changes in the cholinergic system were significantly associated with verbal episodic memory in MCI patients. Instead, only hippocampal volume affected the verbal episodic memory. This concludes that episodic memory dysfunction results primarily from hippocampal neurodegeneration, which is why cholinergic treatments don’t help with verbal fluency among MCI patients. 

However, the research on this topic is still early, and more studies are required to confirm the evidence.

Vagus nerve tone

The vagus nerve is an essential anti-inflammatory nerve that uses acetylcholine. The nerve is the longest nerve in the body and connects your brain to your heart, lungs, gut, and other vital organs. 

The vagus nerve affects our breathing, digestion, and heart rate, which can influence our mental health. However, you need to pay attention to the tone of the vagus nerve, which is the strength of the vagus nerve signal. Higher vagal tone stimulates the parasympathetic nervous system, which helps our body relax and recover faster after stress. 

Low vagus nerve tone is correlated with the incidences of inflammatory diseases, including inflammatory bowel disease (IBD). IBD may worsen due to reduced vagus nerve activity.

There are FDA-approved electrical devices that stimulate the vagus nerve, used to treat depression and epilepsy. However, there are more natural ways to stimulate the vagus nerve.: 

• Socializing and laughing
• Deep and slow breathing 
• Gargling
• Humming
• Singing
• Chanting
• Cold exposure
• Meditation
• Massage
• Exercising

Roles of acetylcholine outside the brain

Besides the brain, acetylcholine has its roles in other parts of the body, as follows:

1. It controls muscle contractions as the primary neurotransmitter in neuromuscular junctions, the synapses (connections) between motor neurons in the spinal cord and muscles. Therefore, acetylcholine is important in activating muscle contractions.
2. It controls autonomic function as part of the autonomic nervous system. It regulates cardiac contractions and blood pressure, glandular secretions, and other physiological functions of various organ systems. 
3. It works as communication messengers between T cells in the immune system. 

Conclusion: 

Acetylcholine is important for many cognitive and bodily functions. Healthy levels of acetylcholine are important for memory, alertness, focus, verbal fluency, etc., and vagus nerve stimulation. Outside the brain, it controls muscle contractions, blood pressure regulation, inflammation, immune responses, and more.

References

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Glutamate is the most abundant neurotransmitter in the brain. It plays various roles in the brain; you can find more information about glutamate and its functions in part 1 of this article.

If you have too much or too little glutamate in your brain, you can experience certain symptoms, which this article covers. These can interfere with your daily tasks and life in general. We will look at the  5 most common symptoms indicating whether you have a glutamate imbalance or not.

Glutamate imbalance is not a disease on its own, but it contributes to many mental health, neurological, and cognitive issues. One of the main causes of this is excess inflammation and oxidative stress, especially in the nervous system. Fortunately, there are many ways to support glutamate balance naturally. See part 3 of this article on how to optimize your glutamate balance. In this article, we’ll cover how to tell if you have too much or too little glutamate.

Symptoms of glutamate imbalances

Glutamate is important for normal brain and cognitive performance. If levels of this neurotransmitter fall below or above the optimal range, certain impairments and neurological dysfunctions can occur.

Symptoms of glutamate imbalances are:

• Inability to focus
• Insomnia
• Anxiety 
• Brain fog
• Chronic pain

Inability to focus

Balanced levels of glutamate are key to maintaining sharp mental focus. Having too little or too much of this chemical messenger can affect an individual’s attention span.

All of us have had this problem at one time or another – the inability to focus on certain tasks or in general. Some nootropics can optimize levels of glutamate in the right parts of the brain; thus helping us to continue with our day and maximize our attention levels.

Insomnia

Another tell-tale sign of glutamate imbalance is insomnia (difficulty in sleeping). This chemical messenger participates in maintaining sleep and wakefulness. 

Glutamate helps to regulate sleep through interaction with different neurons; meaning that there are different phases and circuits that need to be initiated to have a regular sleep cycle.

The reticular formation and the hypothalamus are brain regions that play a role in sleep and consciousness. 

If there are low levels of glutamate in the pontine reticular formation and hypothalamus, interaction with other neurons will be low; this will contribute to insomnia. 

Glutamate also regulates both REM sleep and wakefulness.

Anxiety

Glutamate is a precursor to GABA and they are usually in balance with each other. If glutamate is too high relative to GABA, it will cause anxiety and insomnia. 

Usually, we associate serotonin, dopamine, or other neurotransmitters with anxiety. However, glutamate’s role in this is becoming better understood.

However, glutamate in the right places can decrease anxiety. In clinical trials, glutamatergic drugs have helped with obsessive-compulsive disorder, general anxiety disorders, and social phobia.

A glutamate imbalance can make you anxious. If you struggle with chronic anxiety, consider balancing glutamate and GABA in addition to serotonin and dopamine.

Brain fog

Brain fog is a vague term that refers to the inability to think clearly or recall effectively. Feeling fatigued and being unproductive can also be signs of brain fog – when the brain is not at its top game. It goes hand in hand with impaired memory, attention, and slow cognitive processing. 

Brain fog can be a symptom of an imbalance of certain brain chemicals, specifically glutamate. Too much glutamate can lead to cell death and deprive the brain of antioxidants needed for maximum brain optimization.

This results in an inability to have sharp memory and focus. It can make you feel like you are not 100% “yourself”. Brain fog can be associated with different neurological disorders but a simple cause may be a glutamate imbalance.

Chronic pain

Glutamate plays a vital role in pain sensation and transmission. As such, it has a role in both acute and chronic pain processing. Acute pain is a useful warning signal in the body. However, if pain persists and becomes chronic, it is no longer useful and can be seen as a disease. It can lead to cognitive impairment and even anxiety and depression.

Too high glutamate levels can over-stimulate brain areas such as the amygdala and insula. It disrupts their functioning, leading to perceptions of chronic pain. Therefore, modulating glutamate receptors or lowering brain glutamate levels may help in the treatment of chronic pain. 

I experience these symptoms, what to do next?

Inability to focus, insomnia, anxiety, brain fog, and chronic pain are all signs of having excess or low glutamate levels. Fortunately, it is possible to address the imbalances once you understand the root causes.

References

1. Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. J Neural Transm (Vienna). 2014;121(8):799-817.
2. Shi Y-F, Yu Y-Q. The roles of glutamate in sleep and wakefulness. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013;42(5):583-590.
3. He S, Zhang X, Qu S. Glutamate, glutamate transporters, and circadian rhythm sleep disorders in neurodegenerative diseases. ACS Chem Neurosci. 2019;10(1):175-181.
4. Faraguna U, Ferrucci M, Giorgi FS, Fornai F. Editorial: The functional anatomy of the reticular formation. Front Neuroanat. 2019;13:55.
5. Bear MH, Reddy V, Bollu PC. Neuroanatomy, Hypothalamus. In: StatPearls. StatPearls Publishing; 2021.
6. Watson CJ, Lydic R, Baghdoyan HA. Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation: Glutamate, GABA, and sleep episode duration. J Neurochem. 2011;118(4):571-580.
7. John J, Ramanathan L, Siegel JM. Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R2041-9.
8. Quora. These neurotransmitters are probably keeping you up at night. Forbes Magazine. Published online October 5, 2016. Accessed November 22, 2021. https://www.forbes.com/sites/quora/2016/10/05/these-neurotransmitters-are-probably-keeping-you-up-at-night/
9. Cortese BM, Phan KL. The role of glutamate in anxiety and related disorders. CNS Spectr. 2005;10(10):820-830.
10. Kraal AZ, Arvanitis NR, Jaeger AP, Ellingrod VL. Could dietary glutamate play a role in psychiatric distress? Neuropsychobiology. 2020;79(1):13-19.
11. M J, Stachowicz K, Nowak G, Pilc A. The loss of glutamate-GABA Harmony in anxiety disorders. In: Kalinin V, ed. Anxiety Disorders. InTech; 2011.
12. Kaplan G. Stop Eating These Foods And Clear Up Your Brain! Kaplanclinic.com. Accessed November 22, 2021. https://kaplanclinic.com/stop-eating-these-foods-and-clear-up-your-brain/
13. Rascon G. What is Brain Fog? Symptoms & Treatment Options. Steadymd.com. Published July 16, 2019. Accessed November 22, 2021. https://www.steadymd.com/2019/07/16/brain-fog/
14. Pereira V, Goudet C. Emerging trends in pain modulation by metabotropic glutamate receptors. Front Mol Neurosci. 2018;11:464.
15. French A. Glutamate & Pain. Sfgate.com. Published April 22, 2013. Accessed November 22, 2021. https://healthyeating.sfgate.com/glutamate-pain-8891.html

Glutamate is the most abundant neurotransmitter in your brain. It’s critical for many cognitive processes like learning and memory, among other functions.

Neurotransmitters are molecules that help transmit nerve signals between nerve cells. There are 3 basic types of neurotransmitters which do exactly as their names suggest:

• Excitatory – excite the neurons and set off a positive reaction such as muscle stimulation.
• Inhibitory – inhibit nerve responses or reduce the intensity of nerve signals in the receiving neurons.
• Modulatory – these can have different effects on different neurons, depending the context

Glutamate is the main excitatory neurotransmitter. You have numerous glutamate receptors throughout your brain and spinal cord. 

Even though glutamate is essential, too much of it can jam neuronal functions, killing neurons and causing brain fog. Therefore, to optimize your brain function and health, you want to have just the right levels of glutamate in the right brain regions. Too low and your brain won’t function right. Too high and your neurons die. In fact, excess glutamate in the wrong brain regions contributes to many cognitive, psychiatric, and neurological disorders.

There are many ways to optimize brain glutamate levels naturally. If you are using nootropics or want to start, it is vital to learn about glutamate, its benefits, and its negative effects. 

More information about factors and symptoms of glutamate imbalance and how to optimize glutamate levels can be found in parts 2 and 3 of this article. 

What is glutamate?

Glutamate is an amino acid which also works as a neurotransmitter in your brain. The neurons that release glutamate are called glutamatergic neurons and the neuronal pathways that rely on glutamate are called glutamatergic pathways.

Both nerve cells and glial cells (non-nerve housekeeping cells in the brain) work together to maintain healthy brain glutamate levels in the right brain regions.

One of the ways your brain ensures that glutamate functions right is by having the right glutamate receptors. This is also why nootropics work by targeting one receptor type but not the others, so we will cover different glutamate receptors and what they do.

Glutamate receptors

There is a lot of glutamate in the brain, so aside from putting glutamate in the right compartments, your brain also needs to correctly route the nerve signals. Different glutamate receptors make it possible to achieve this. There are two families of glutamate receptors: ionotropic and metabotropic. 

• Ionotropic receptors open a channel into the nerve cell once glutamate binds to them. The open channel then allows ions to flow in, which either strengthens or weakens the electrical nerve impulses in the receiving neurons. These include NMDA, AMPA, and Kainate receptors.
• Metabotropic receptors signal through other pathways to increase the electrical impulses inside the receiving neurons. These include mGluR receptors.

NMDA

N-methyl-D-aspartate (NMDA) – is an ionotropic receptor that plays an important role in memory and learning. Glutamate causes excitatory activity through NMDA. Abnormal levels of NMDA receptor activation can lead to cell death, neuronal dysfunction, and problems with learning and memory.

You may have excess NMDA receptor activation when overwhelming amounts of information can make it harder to learn. Increasing the activation of NMDA receptors by increasing glutamate in the right brain regions can improve memory and learning. 

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors consist of different subunits. AMPA receptors are responsible for brain plasticity, learning, and certain neurological diseases. 

AMPA receptors improve learning and memory differently than NMDA. The increase of AMPA ion channel receptors in the membrane stimulates better cognitive functions. 

Low AMPA receptors are associated with learning impairment and the inability to remember new information. Increasing AMPA receptors in the postsynaptic membrane increases cognitive abilities.

Kainate

Kainate receptors are the “bad” ionotropic glutamate receptors you don’t want to activate. To maximize your learning and memory, you want to inhibit kainate receptors and tune up the other ionotropic receptors.

Kainic acid activates kainate receptors. It is a strong excitatory amino acid neurotransmitter that activates glutamate receptors. Unlike NMDA and AMPA receptors, kainate receptors are activated both in the receiving and transmitting neurons (both pre and post synapses).  The kainate receptors also play a role in synaptic plasticity and induction of NMDA and AMPA receptors.

Although kainate receptors are found throughout the brain, it’s important for programming the amygdala, your memory center. Your amygdala is responsible for emotional behaviour, memory, and autonomic function, especially in the context of fear and traumas. However, certain amounts of these receptors have to be activated to initiate the amygdala’s activity.  

Furthermore, kainate activation may contribute to some neurological disorders such as :

• Epilepsy 
• Depression
• Bipolar disorder 
• Autism 
• Huntington’s disease 
• Schizophrenia 

Therefore, it is better to keep your kainate activation low to maximize memory, learning, and overall neurologic health. Instead, you want to focus on activating NMDA and AMPA receptors.

mGluR

Metabotropic glutamate receptors are divided into different groups based on their similarity. The mGluR receptor is the one most extensively studied.

mGluR controls glutamate activity by G-protein cell signaling. These receptors play a role in brain plasticity and help in treating several neurological disorders.

Furthermore, high production of these receptors aids in memory and learning (which is of concern to us), while low levels can result in depression. High levels of glutamate are needed to activate these receptors. 

Important roles of glutamate for cognitive performance

Here are how glutamate plays a role in each of these crucial brain processes:

Synaptic plasticity

Synapses are the connections between nerve cells in the brain. These connections are not static but can change, i.e., they are “plastic”. Synaptic plasticity refers to the strengthening or weakening of synapses when we learn or unlearn something. It is a well-known phenomenon that the brain physically changes when we read, learn, or memorize certain information.

The saying, “Neurons that fire together wire together” perfectly explains this. When two nerve cells are activated together constantly, they make stronger connections.

Memory

Glutamate also plays a vital role in memory formation and other cognitive functions. Memory is such a broad and fascinating concept that sometimes learning about its processes can feel like you are watching the movie Inception, where you start to question what’s real and what isn’t. 

When you think of a thought or idea, your nerve cells fire in neural circuits. Once you repeat the thought, the connections between these circuits become stronger, allowing memory to form. 

This is where glutamate steps in because it helps strengthen the connections between these neurons, enhancing the process of memory formation and retrieval. So, the next time you try to remember something, keep in mind that glutamate is working hard to help you out.  

Long-term potentiation

As the name might indicate, long-term potentiation refers to when two neurons strengthen their connections based on frequent stimulation.

“Practise makes perfect” rings very true in the case of long-term potentiation between neurons. Similarly to what was mentioned in synaptic plasticity, when the brain is used to actively retrieve information, neurons light up and form more connections. So, the more we use our neurons, the stronger the connections between them become. 

NMDA is a glutamate receptor which plays a key role in memory formation. Studies that have been done on rats have shown that NMDA is present when long-term potentiation is being formed.

Cognitive functions: decision making and problem solving

     Cognitive function is a term that encompasses decision-making, thinking, problem-solving, and many other vital processes.

Think of a situation where you are put on the spot and have to come up with a quick decision. Glutamate can signal the brain to activate cognitive functions that will aid in decision-making. This neurotransmitter can quickly send signals to the responsible regions of the brain, making sure that the cognitive functions are properly utilized.

Emotions

Glutamate is also important for emotions. For example, it may have a central role in how fears are formed and broken down. Excess glutamate in the brain may contribute to anxiety while blocking glutamate receptors sometimes help with anxiety symptoms.

Sensory information

The five senses: sound, taste, sight, smell, and touch make up our sensory information and glutamate helps us to process this. Neurotransmitters in the sensory ganglia provide this  remarkable ability to work out the different stimuli from the environment.

To experience these sensations, nerve signals travel through the somatosensory pathway through the sensory ganglion, up the spinal cord, and into the somatosensory cortex region in the brain.

The sensory ganglia are structures that allow the central nervous system to receive sensory information. Glutamate is a key neurotransmitter in sensory ganglia, making it a vital part of sensory information processing.

The somatosensory cortex is a region of the brain that receives and processes all sensory information from the entire body. This region is further divided into primary and secondary somatosensory cortices. The primary somatosensory cortex functions:

• Localization of sensation
• Pressure perception
• Weight perception
• Shape perception
• Feeling texture

Primary sensory neurons help convert your senses into neural impulses, which is then transmitted to the central nervous system. 

The primary somatosensory cortex receives incoming stimuli through a simple circuit relayed by only two subcortical nuclei in the brainstem and thalamus. 

All primary sensory neurons have glutamate receptors and transporters to communicate with glutamate. Glutamate mediates excitatory neurotransmission in brain networks that are important for sensory perception, memory, and sensorimotor control. 

Understanding how glutamate works is essential for understanding how the body responds to external factors, and what can be done to possibly lessen painful stimuli.

Coordinating with other neurotransmitters

Your nervous system involves well-choreographed dances between various neurotransmitters and neuronal pathways. 

Glutamate is a key player in these dances. It helps coordinate these neurotransmitters, receptors, and transporters to ensure that the brain works properly. 

For example, glutamate interacts with the stress neurotransmitter norepinephrine in PTSD (post-traumatic stress disorder), affecting cognitive function, emotions and senses in PTSD patients. 

Another important point to mention is that glutamate acts as a mediator in different pathways, it is even involved in killing off certain cells, which can play a major role in various systems.

Everything needs to be kept in balance for the system to work as it should. Imbalances can often be corrected and the various problems solved as a result. 

In conclusion

Glutamate is a vital neurotransmitter in our brains, as it plays a role in several cognitive processes such as memory, learning, emotions, and long-term potentiation. It also influences synaptic plasticity and coordinates with other neurotransmitters in the brain.

However, too much of it can kill neurons. Imbalance in glutamate levels results in various cognitive impairments (you can find more about this here). Glutamate receptors are key when it comes to glutamate levels.

However, don’t worry! There are many natural ways to balance glutamate levels and optimize your brain and cognition. Read more about how to optimize your glutamate levels here.

References

There was one little experiment one day, the carbon arc furnace, which blew up… and seared my tear ducts (the reason I’m wearing these patches over my eyes in the picture on the right). 

Six weeks later, when they pulled the patches off, I could see fine. And life was the same. I moved on to the next experiment. 

My mom would have to ask time and time again for me to come to dinner or to remind me that it’s time for bed. It wasn’t because I was abstinent. It was because I was so deeply ingrained in whatever I was doing.

Fast forward a few years, and I was both volunteered and requested to take Accutane in mega doses. This changed everything for the worse.

I could no longer focus for long periods. I always felt a bit of a fog. My energy declined over time as well.

I was a good athlete, but I slowly lost my drive to win.

Fast forward to 2021, and I can focus like a machine for 16 hours a day. I can deliver whatever life demands of me thanks to having an optimized brain.

With the help of nootropics, I don’t experience depression. I get more done in 4 hours than I used to complete in 4 days. Best of all: I have a blast doing it.

But that’s not all: every performance aspect of my life has improved. That means: mind, body, energy, sex, and sleep.

Here’s an exciting aspect of this: your horizon for adjustment and tweaking of your performance is infinite. 

Think: what if you could improve some area of your mind and body every day… Where would you be in a year?

• Would you become a partner in your law firm?
• Would you become a top trader on Wall Street?
• Move from the mailroom to a VP position?
• Actually live Tim Ferriss’s 4-Hour Workweek?

I’m not saying you and I will become Eddie Morra overnight. But I am quite confident you and I are barely touching our potential.

When we were beginning to test our original base formula in 2008, we knew three things:

1. A clear, deep, fast, and connected mind makes better decisions. Those decisions can dramatically affect your results in life.

2. A tireless mind and body can act on those decisions. Action creates momentum. 

3. Good decisions with action create success, however you define it. Whether that’s changing the world. Changing your mind. Or simply multitasking as you’re changing a diaper.

Change– and life improvements– take drive, courage, and energy. Courage is best leveraged when you can anticipate outcomes. Anticipating outcomes requires quickly thinking through the myriad of variables that impinge on our objectives.

Make sense?

It’s not just about being smarter at Monopoly or winning at Twister.

It’s about operating at a higher level, amplifying your strengths, and then turning them into super powers… And enjoying the journey.

Stress comes from not understanding the actual likelihood of a potential outcome. It comes from falsely anticipating and fearing what might happen. 

On the flip side: understanding, managing, and embracing what you can control gives you power. This is where high cognitive function, strong and resilient physical capacity, and positive, anticipatory thinking comes into play.

This is why I take Nootropics every day. And why I believe it can be the best game-changer for you too.

Watch this video and learn how to use these breakthrough brain stacks to architect and hack the ultimate mental states for productivity, creativity, and happiness.

Because being sick and suboptimal sucks. And being your best and cycling into Superhuman territory is a gift that, once experienced, is something that will change your life forever. 

And, at the cost of a Starbucks or two a day, it’s one of the most cost effective, lifetime enhancements I could ever hope for.

Oh, and if like me you’ve struggled with focus, here’s a Powermove: FOCUS-WINDOWS…

Focus-windows are by definition an awesome FOCUS TOOL. The goal is to: STICK WITH THAT ONE THING until the focus-window is done.

At first, it will be hard. Your brain is going to want to escape. That’s your brain’s focus weakness coming out. It wants you to relieve it of the strain.

If you just CAN’T stay focused for an hour, then try shortening the focus-window to 30 minutes to start. Less than 30 minutes is not enough to get into a flow state. With time, effort and consistency, your mental endurance will go up. 

If you’re ready to start your journey to apex brain performance, you can select the stack that best suits your goals. Click HERE to learn more about them and select yours.