Author: Mr. Noots

Just like any other part of our body, the brain requires effective mechanisms to detoxify and maintain optimal function.

By integrating simple strategies into our daily routines, you can support your brain’s natural detoxification process, leading to clearer thinking, improved focus, and overall mental well-being.

What is Brain Detoxification?

Every day, your brain naturally detoxes to keep itself healthy. Brain detoxification is the process by which the brain clears out toxins, waste products, and other substances that may accumulate and interfere with normal functioning. Like the rest of the body, the brain has mechanisms to remove waste and maintain health.

What is the Brain Detoxification System?

Your brain needs to maintain homeostasis (balanced) for optimal function. The great news is that your body already has a system to continuously move waste. It’s called your glymphatic system. 

The glymphatic system, a network in the brain, facilitates waste clearance and fluid transport, employing fluid movement around blood vessels and through a type of brain cell called astrocytes. This system operates by circulating cerebrospinal fluid (CSF) throughout the brain, which gathers waste and carries it away for elimination from the body.

Working alongside are glial cells, specialized brain cells, which collaborate with a network of channels surrounding blood vessels. Together, they eliminate waste products while supplying essential nutrients such as glucose, fats, and neuromodulators to the brain.

These channels, constructed by astroglial cells, form tunnels through which substances can freely move, ensuring efficient brain function and maintenance. 

The glymphatic system is constantly working to remove waste and substances that can be toxic from your brain. Keep in mind the system is the most active when we’re asleep, especially during deep sleep stages.

When we sleep, a chemical called norepinephrine levels drop, which expands the spaces around brain cells. This expansion makes fluid flow through and wash away waste products easier. 

During the deepest stage of sleep, also called slow-wave sleep, the brain produces slow, rhythmic waves that help move fluid even more efficiently, leading to better brain cleaning. 

How to Detox Your Brain

Your brain naturally detoxes itself every day, but it’s possible your brain detoxification isn’t working optimally. Supporting brain detoxification to work its best involves more than just quick-fix methods. 

Instead, it revolves around nurturing and supporting the glymphatic system by adopting healthy habits. Let’s look at some changes you may want to consider to promote clarity, focus, and overall brain health.

Sleep

Because the glymphatic system does most of its work while you sleep, it’s critical to get enough high-quality sleep.

Deep Sleep

A study explored the effects of sleep on cerebrospinal fluid (CSF) flow. Researchers used brain imaging techniques like Bold fMRI, EEG, and CSF measurements to determine when the brain is busiest during sleep.

When people were awake, cerebrospinal fluid (CSF) flow in the brain was rhythmic but not very strong.

During sleep, especially deep sleep, the flow of CSF became stronger and more pulsating, bringing more CSF into the brain than when awake. This increased flow helps clean the brain and provides more oxygen to brain cells.

Deep sleep is so important to keep our brains healthy, but how can we promote deep sleep? There are six major ways:

1. Optimize light: Light dictates your circadian rhythm, so make sure to sleep in total darkness and avoid blue light at night. 

2. Optimize Temperature: Your body wakes up when it gets too hot. Make sure to keep your bedroom cool, and if that’s not enough, look into purchasing a cooling mattress pad. 

3. Avoid Pressure Points: Your body will wake you up if there is any constricted blood flow. A memory foam mattress is a great option for side sleepers to relieve pressure. A healthier option is an organic tree sap mattress.

4. Be Consistent and Early: To optimize your sleep, listen to your body’s cues and head to bed when you feel tired to avoid experiencing a second wind that could disrupt your sleep. Consistency is key to supporting your circadian rhythm, so maintain a regular sleep schedule whenever possible.

5. Meal Timing: Avoid eating within 2-3 hours of bedtime to ensure your stomach is empty before sleep. 

6. Master Your Brainwaves: Boost your alpha brain waves and lower your beta brain waves before sleep. Techniques like mindfulness meditation, deep breathing exercises, or progressive muscle relaxation can help promote relaxation and ease. This makes it easier to fall asleep and experience restorative sleep throughout the night.

For more ideas on how to support deep sleep, check out this article.

Sleep Position

You may also better support your glymphatic system by sleeping in the right position. 

This idea was first discovered in an animal study. The study wanted to see if sleeping in different positions affected how the glymphatic system works. Subjects were kept still in three different sleeping positions: on their back, on their belly, and on their side.

Using MRI scans, researchers observed that subjects lying on their side had better brain waste clearance than those lying on their back or belly. Brain waste clearance was slower and less efficient when subjects were on their belly.

A later study in humans explored the relationship between sleep position and normal age-related cognitive decline. 

Participants with cognitive decline tended to sleep on their backs more frequently than those with normal cognitive functions and for more than two hours per night.

Exercise

Regular exercise may help promote brain health and support the glymphatic system’s ability to remove toxins and waste from the brain. It does this in a couple of ways.

First, exercise stimulates the production of certain molecules to help regulate the glymphatic system’s activity. This enhances its efficiency in clearing waste products from the brain. 

A study explored this using an animal model. Older mice exercised by running on a wheel. To see if exercise helped their brains, researchers tested their ability to remember locations in a water maze.

Over six weeks, voluntary running:

• Improved brain protein balance
• Reduced inflammation
• Enhanced cognition

Exercise boosted glymphatic waste clearance. Researchers injected a special dye into the space around the brain and spine, and then took pictures to see how the dye moved through the brain and how fast the brain got rid of it.

Initially, the dye levels were the same in the running and non-running mice. However, dye intensity peaked in the running group at 15 minutes before gradually diminishing. At 30 and 60 minutes, the running subjects had significantly less dye than those not running, indicating accelerated clearance.

Possibly due to increased glymphatic system activity, amyloid-beta buildup (known for its role in cognitive decline and neurodegeneration) was lower in running subjects. It also accelerated waste removal by increasing fluid movement around brain cells and raised levels of AQP4, a protein aiding fluid flow in the brain.

Regular exercise is also associated with improved sleep quality, which we’ve already covered is essential for optimal glymphatic system function. 

A meta-analysis of 35 clinical trials, including over 3,500 participants, explored the effects of exercise on sleep quality. Moderate-intensity muscle endurance training combined with walking was the most effective exercise for enhancing sleep quality. The exercise was 40- to 60-minute sessions, two to seven times a week for at least 8 weeks.

Another meta-analysis of 13 studies with 2,600 patients examined the effects of physical activity on sleep. The studies included a range of exercises including:

• Yoga
• Cycling
• Walking
• Pilates
• Elastic bands
• Healthy Beat Acupunch 

In all studies included, exercise improved sleep quality. The strongest improvements in sleep quality were associated with participation in an exercise program at a facility rather than home-based.

Whatever exercise you undertake, it’s important to get moving. The World Health Organization recommends getting at least 150 minutes of moderate exercise or 75 minutes of vigorous exercise weekly.

Omega-3s

Your brain contains many omega-3 polyunsaturated fatty acids (n3-PUFAs), known for their anti-inflammatory properties. Substances like amyloid-beta, linked to cognitive decline, affect learning and memory, which can be improved by these fatty acids.

Observational studies indicate that eating a diet high in omega-3s may contribute to maintaining cognitive function, preventing its decline in the early stages. 

In studies conducted on mice, omega-3 fatty acids demonstrated an ability to enhance the brain’s natural waste removal system, effectively clearing out harmful substances such as beta-amyloid.

While human studies haven’t looked directly at the effects of omega-3s on the glymphatic system, they have explored the effects of omega-3s on brain function.

A review of nine trials including over 1,000 participants found that consuming omega-3s seems to alter cognitive processing and improve mental performance. Taking omega-3 supplements led to:

• Increased learning
• Memory
• Cognitive well-being
• Increased blood flow in the brain

The FDA advises a daily intake of 3 grams of omega-3, with dietary supplements providing up to 2 grams per day.

Some of the best sources of Omega-3s outside of supplements include:

• Fish and other seafood (especially cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines)
• Nuts and seeds (such as flaxseed, chia seeds, and walnuts)

Intermittent Fasting

Intermittent fasting, alternating between eating and fasting periods lasting from 12 to 48 hours, may also support the glymphatic system.

In the brain, there are two forms of a protein called AQP4: a long one and a short one. They combine to form groups on the outer layer of certain brain cells.

When you fast occasionally, it reduces the amount of the long form of AQP4, which changes the ratio of these two forms. This change helps move more of the AQP4 protein to specific brain areas, improving the brain’s ability to clear waste.

Minimize Toxin Exposure

Because your glymphatic system is responsible for clearing waste, it’s important to do what you can not to overburden it.

Avoiding toxins in air, food, water, home, skincare, and cosmetic products can help prevent the accumulation of harmful substances in the body, reducing the workload on the glymphatic system and promoting its proper functioning. 

Here are some simple strategies to incorporate into your daily life to avoid toxin exposure:

1. Choose natural sweeteners to avoid the possible gut-altering effects of artificial sweeteners
2. Eat organic whenever possible; at a minimum, avoid the dirty dozen
3. Drink filtered water
4. Try dry brushing – it may stimulate the lymphatic system to remove cell waste and environmental toxins
5. Switch out your plastic for glass
6. Eat grass-fed/wild meat
7. Sweat a lot, such as with infrared saunas
8. Switch to non-toxic home and body care products. 
9. Load up on probiotics, like P3-OM, when taking antibiotics

Get even more strategies from our book, From Sick to Superhuman. 

Consider Supplements

Since quality sleep plays a vital role in the proper functioning of the glymphatic system, if you’re having trouble getting good sleep, think about trying supplements that can help support healthy sleep patterns.

Sleep Breakthrough

Sleep Breakthrough gives your body the precursors to melatonin and the molecules that help your body produce melatonin naturally. It comes in two different formulas.

One of the key ingredients, magnolia bark, shows promise in animal studies. It contains honokoil,  which helped subjects fall asleep faster and increased the time they spent in a type of sleep called non-REM sleep.

Magnesium Breakthrough

Supplementing with magnesium may improve how quickly you fall asleep and how well you sleep. 

A study of 46 individuals struggling with sleep explored the effects of magnesium supplementation on sleep. Participants took 500 mg of magnesium daily for eight weeks.

Those taking magnesium experienced:

• Increased sleep time
• Falling asleep faster
• Reduced early morning awakening
• Increased melatonin levels

Magnesium Breakthrough contains seven forms of magnesium specially formulated to reach every tissue in your body to provide maximum health benefits.

Mental Reboot PM

Mental Reboot PM is formulated to support the brain’s natural restorative processes during sleep. It includes key ingredients supporting the glymphatic system like chlorella. 

Chlorella is a single-celled freshwater algae rich in proteins, vitamins, minerals, and fiber. It contains various nutrients directly supporting brain health, including omega-3 fatty acids, B vitamins, and minerals. 

An animal study exploring the effects of chlorella showed promising results for brain and memory function. Subjects taking chlorella short-chain peptides demonstrated improved memory and learning and mitigated age-related brain cell loss.

Conclusion

By embracing practices that support the glymphatic system’s function, you can optimize your brain health and unlock your full cognitive potential. Take steps now to prioritize brain detoxification:

• Prioritize quality sleep
• Stay active with regular exercise – aim for at least 150 minutes per week
• Get omega-3s through omega-rich foods and supplement if needed
• Minimize your toxin exposure
• Consider taking sleep and brain-supporting supplements like Sleep Breakthrough, Magnesium Breakthrough, and Mental Reboot PM

References:

1. Gao Y, Liu K, Zhu J. Glymphatic system: an emerging therapeutic approach for neurological disorders. Front Mol Neurosci. 2023;16. doi:10.3389/fnmol.2023.1138769
2. Reddy OC, van der Werf YD. The sleeping brain: Harnessing the power of the glymphatic system through lifestyle choices. Brain Sci. 2020;10(11):868. doi:10.3390/brainsci10110868
3. Fultz NE, Bonmassar G, Setsompop K, et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science. 2019;366(6465):628-631. doi:10.1126/science.aax5440
4. Lee H, Xie L, Yu M, et al. The effect of body posture on brain glymphatic transport. J Neurosci. 2015;35(31):11034-11044. doi:10.1523/jneurosci.1625-15.2015
5. Levendowski DJ, Gamaldo C, St. Louis EK, et al. Head position during sleep: Potential implications for patients with neurodegenerative disease. J Alzheimers Dis. 2019;67(2):631-638. doi:10.3233/jad-180697
6. He XF, Liu DX, Zhang Q, et al. Voluntary exercise promotes glymphatic clearance of amyloid beta and reduces the activation of astrocytes and microglia in aged mice. Front Mol Neurosci. 2017;10. doi:10.3389/fnmol.2017.00144
7. Hasan F, Tu YK, Lin CM, et al. Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis. Sleep Med Rev. 2022;65(101673):101673. doi:10.1016/j.smrv.2022.101673
8. Solis-Navarro L, Masot O, Torres-Castro R, et al. Effects on sleep quality of physical exercise programs in older adults: A systematic review and meta-analysis. Clocks Sleep. 2023;5(2):152-166. doi:10.3390/clockssleep5020014
9. Physical activity. Who.int. Accessed March 13, 2024. https://www.who.int/news-room/fact-sheets/detail/physical-activity
10. Ren H, Luo C, Feng Y, et al. Omega‐3 polyunsaturated fatty acids promote amyloid‐β clearance from the brain through mediating the function of the glymphatic system. FASEB J. 2017;31(1):282-293. doi:10.1096/fj.201600896
11. Dighriri IM, Alsubaie AM, Hakami FM, et al. Effects of omega-3 polyunsaturated fatty acids on brain functions: A systematic review. Cureus. 2022;14(10). doi:10.7759/cureus.30091
12. Krupa K, Fritz K, Parmar M. Omega-3 Fatty Acids. StatPearls Publishing; 2023.
13. Omega-3 fatty acids. Nih.gov. Accessed March 13, 2024. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/
14. Wang DJJ, Hua J, Cao D, Ho ML. Neurofluids and the glymphatic system: anatomy, physiology, and imaging. Br J Radiol. 2023;96(1151). doi:10.1259/bjr.20230016
15. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-186. doi:10.1038/nature13793
16. Qu WM, Yue XF, Sun Y, et al. Honokiol promotes non‐rapid eye movement sleep via the benzodiazepine site of the GABAA receptor in mice. Br J Pharmacol. 2012;167(3):587-598. doi:10.1111/j.1476-5381.2012.02010.x
    [/custom-reference]
17. Wang SM, Chuu JJ, Lee CK, Chang CY. Exploring the therapeutic efficacy of Chlorella pyrenoidosa peptides in ameliorating Alzheimer’s disease. Heliyon. 2023;9(5):e15406. doi:10.1016/j.heliyon.2023.e15406
18. Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences. 2012;17(12):1161.

What are psychobiotic supplements?

Psychobiotics are probiotics and prebiotics that can deliver mental health and cognitive benefits through the gut-brain axis. Researchers are still understanding all the ways that gut bacteria can influence your mind, here are some ways by which gut bacteria and probiotics do so:

• Producing neurotransmitters – neurotransmitters in the gut may not directly increase neurotransmitters in your brain, but they can work through your gut neurons to influence your brain functions.
• Producing other brain-influencing substances, such as short-chain fatty acids and neurotransmitter metabolites.
• Communicating with your brain through the vagus nerve.
• Balancing inflammation and oxidative stress levels in your entire body. Inflammation and oxidative stress can interfere with your brain function, causing sluggish brain and bad mood.

Many herbs also work with gut flora to activate certain substances, or work by improving the gut flora, such as the Chaihu Shugan San formula in our Cognibiotics.

Keep in mind most of these psychobiotic studies are in rodents. In most cases, to reap the same benefits, you’d need to pick probiotic formulations that are optimized to survive your digestion rather than ones that just have these strains.

Dosages should be in the billions to ten billions. However, spore-based bacteria or some preparations are made to survive digestive conditions and deliver benefits at a lower dose.

The results also likely vary from person to person, as a meta-analysis of clinical trials for mood-enhancing effects of probiotics showed significant but likely heterogeneous.

This is why we formulated Cognibiotics with the most powerful psychobiotic strains and cognitive-enhancing Chinese herbs that synergize with probiotics.

How do probiotics for mental health work?

Supporting Healthy Stress Response (HPA Axis)

In rodents, supplementation with these strains reduced cortisol and mitigated some stress-related symptoms:

• L. plantarum
• L. helveticus
• L. fermentum
• L. rhamnosus
• L. casei

B. longum 1714 – A randomized, double-blinded placebo-controlled trial tested 40 subjects on B. longum 1714 vs placebo for 4 weeks. All subjects played the Cyberball game to simulate social stress.

Magnetoencephalography (a magnet non-invasive brainwave measurement) found that the probiotic group had increased theta brain wave in the frontal and cingulate cortex, and lower beta brainwave in the hippocampus, fusiform, and temporal cortex.

These changes are associated with subjective vitality and reduced mental fatigue.

In another clinical trial, 22 subjects completed cognitive assessments with EEG brainwave measurements after a cold pressor test, either after taking 109 (1 billion) CFU B. longum 1417 or a placebo.

The probiotic groups had less cortisol increase and subjective situational anxiety response along with reduced stress and improved memory.

L. plantarum PS128 reduced inflammation and corticosterone levels, while increasing dopamine, thus reducing traits resembling mood issues in mice.

Improving Neurotransmitter Balance

• L. plantarum, L. helveticus, L. fermentum, L. rhamnosus, and B. infantis change animal behaviors partly by influencing levels of neurotransmitters serotonin, dopamine, and GABA in the brain. These good bacteria also crowd out the bad bacteria and reduce the enzymes that may convert healthy neurotransmitters into neurotoxic metabolites.
• Bifidobacterium breve CCFM1025 upregulates tryptophan, 5-HTP, and serotonin in the gut.

Producing Neurotransmitters in the Gut

Many probiotics produce neurotransmitters. However, neurotransmitters and similar molecules in the gut may not increase neurotransmitters in the brain.

Most neurotransmitters are too large to cross the blood-brain barrier, therefore neurotransmitters in the brain are produced and maintained separately from those in the gut.

While taking GABA orally doesn’t increase brain GABA, most people will find relaxation effects. Oral GABA helps you feel relaxed through GABA receptors in your gut, and presumably, GABA produced by your gut bacteria works similarly

Here, we’re only including probiotic strains that are generally recognized as safe and available in dietary supplements. Neurotransmitter production is based on high-performance liquid chromatography detection.

Supporting Neurogenesis and Neuroplasticity With Prebiotics

Prebiotic fermentation by good bacteria produces short-chain fatty acids that can induce brain fertilizer proteins, such as BDNF. These can have potent cognitive, mood-enhancing, and anti-aging benefits for your brain.

In rats, gavaging (force-feeding) with prebiotics called fructooligosaccharides (FOS) and galactooligosaccharides (GOS), GOS increased markers of neuroplasticity and glutamate signaling in the hippocampus.

When the researchers applied the plasma of rats that had GOS to human nerve cells, the nerve cells produced more BDNF.

Protecting the Brain Against Oxidative Stress

L. acidophilus, B. lactis, and L. fermentum increase antioxidant enzymes and improve cognitive function in rats with elevated oxidative stress.

Our internal lab tests detected some antioxidant activities with P3-OM and probiotic strains in Cognibiotics.

Stimulating the Vagus Nerve

There have been multiple rodent studies that observe neurochemical changes in the brain after the animals eat probiotics. Cutting the vagus nerve effectively prevents these neurochemical changes from occurring.

Lactobacillus rhamnosus JB1 is one such bacteria strain that significantly stimulates the vagus nerve.

Conclusion:

Your gut flora can play powerful roles in your mindset, mental health, and cognitive functions so it’s important to feed them right. Also, consider adding research-backed psychobiotics like Cognibiotics to your mood and cognitive enhancement toolbox.

References:

1. Bermúdez-Humarán, L. G., Salinas, E., Ortiz, G. G., Ramirez-Jirano, L. J., Morales, J. A. & Bitzer-Quintero, O. K. (2019). From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis. Nutrients, 11(4). https://doi.org/10.3390/nu11040890
2. Kim, S.-H., Han, J., Seog, D.-H., Chung, J.-Y., Kim, N., Hong Park, Y. & Lee, S. K. (2005). Antidepressant effect of Chaihu-Shugan-San extract and its constituents in rat models of depression. Life Sciences, 76(11), 1297–1306.
3. Zhu, H., Tian, P., Zhao, J., Zhang, H., Wang, G. & Chen, W. (2022). A psychobiotic approach for mental health: A systematic review and meta-analysis. Journal of Functional Foods, 91, 104999.
4. Liu, Y. W. et al. Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain Res. 1631, 1–12 (2016).
5. Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J. & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America, 108(38), 16050–16055.
6. Ohland, C. L., Kish, L., Bell, H., Thiesen, A., Hotte, N., Pankiv, E. & Madsen, K. L. (2013). Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology, 38(9), 1738–1747.
7. Wang, T., Hu, X., Liang, S., Li, W., Wu, X., Wang, L. & Jin, F. (2015). Lactobacillus fermentum NS9 restores the antibiotic induced physiological and psychological abnormalities in rats. Beneficial Microbes, 6(5), 707–717
8. Takada, M., Nishida, K., Kataoka-Kato, A., Gondo, Y., Ishikawa, H., Suda, K., Kawai, M., Hoshi, R., Watanabe, O., Igarashi, T., Kuwano, Y., Miyazaki, K. & Rokutan, K. (2016). Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 28(7), 1027–1036.
9. Wang, H., Braun, C., Murphy, E. F. & Enck, P. (2019). Bifidobacterium longum 1714^TM Strain Modulates Brain Activity of Healthy Volunteers During Social Stress. The American Journal of Gastroenterology, 114(7), 1152–1162.
10. Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J. F., Dinan, T. G. & Clarke, G. (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational Psychiatry, 6(11), e939.
11. Yafei Liu, Haijian Yang, Chao Jiang, Chao Yang, A scalable fully implicit method with adaptive time stepping for unsteady compressible inviscid flows, Computers & Structures, Volume 176, 2016, Pages 1-12, ISSN 0045-7949.
12. Ohland, C. L., Kish, L., Bell, H., Thiesen, A., Hotte, N., Pankiv, E. & Madsen, K. L. (2013). Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology, 38(9), 1738–1747.
13. Wang, H., Lee, I.-S., Braun, C. & Enck, P. (2016). Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review. Journal of Neurogastroenterology and Motility, 22(4), 589–605.
14. Dehhaghi, M., Kazemi Shariat Panahi, H. & Guillemin, G. J. (2019). Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status. International Journal of Tryptophan Research: IJTR, 12, 1178646919852996.
15. Chen, G., Zhou, S., Chen, Q., Liu, M., Dong, M., Hou, J. & Zhou, B. (2022). Tryptophan-5-HT pathway disorder was uncovered in the olfactory bulb of a depression mice model by metabolomic analysis. Frontiers in Molecular Neuroscience, 15, 965697.
16. Boonstra, E., de Kleijn, R., Colzato, L. S., Alkemade, A., Forstmann, B. U., & Nieuwenhuis, S. (2015). Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Frontiers in psychology, 6, 1520. https://doi.org/10.3389/fpsyg.2015.01520
17. Heyck, M. & Ibarra, A. (2019). Microbiota and memory: A symbiotic therapy to counter cognitive decline? Brain Circulation, 5(3), 124–129.
18. Savignac, H. M., Corona, G., Mills, H., Chen, L., Spencer, J. P. E., Tzortzis, G. & Burnet, P. W. J. (2013). Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochemistry International, 63(8), 756–764.
19. Davari, S., Talaei, S. A., Alaei, H. & Salami, M. (2013). Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience, 240, 287–296.
20. Perez-Burgos, A., Wang, B., Mao, Y.-K., Mistry, B., McVey Neufeld, K.-A., Bienenstock, J. & Kunze, W. (2013). Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. American Journal of Physiology. Gastrointestinal and Liver Physiology, 304(2), G211–G220.

In this article, you’ll learn about neuroplasticity, neuroplasticity types, and diet and lifestyle tips that enhance neuroplasticity. In the next article, we’ll cover powerful neuroplasticity-enhancing supplements.

What Is Neuroplasticity?

Neuroplasticity, often referred to as brain plasticity or neural plasticity, is the brain’s remarkable ability to reorganize itself, both functionally and structurally. This means your brain’s structure and function do not remain fixed after a certain age; rather the brain has an ever-changing nature and it is capable of growing and adapting. 

Neuroplasticity occurs throughout an individual’s lifespan in response to:

1. Experiences
2. Learning
3. Environmental changes
4. Injury 

Synapses play a key role in allowing neuroplasticity to occur. A synapse is a specialized junction that enables communication between two neurons. It is the point where one neuron transmits information to another neuron, allowing signals to pass from one cell to the next in the intricate network of the nervous system.

Synapses also exhibit plasticity (synaptic plasticity), which means they can change in strength and effectiveness over time. This allows the brain to rewire its circuits and optimize its responses based on experiences and learning. 

Types of Neuroplasticity

There are two main types of neuroplasticity: structural neuroplasticity and functional neuroplasticity.

Structural Neuroplasticity

Structural neuroplasticity refers to the physical changes in the brain’s architecture, particularly in terms of its neural connections and organization. This type of neuroplasticity involves modifications to the actual structure of neurons and their interconnections, including: 

• Synaptogenesis, the formation of new synapses 
• The strengthening of existing synapses
• Synaptic pruning, the elimination of unused or weaker synapses 

These structural changes contribute to the rewiring of neural circuits and play a pivotal role in learning, memory, and adaptation. Structural neuroplasticity is especially prominent in utero and during childhood, but it continues throughout life, allowing the brain to adapt to new experiences, learn new skills, and recover from injuries.

Functional Neuroplasticity

Functional neuroplasticity involves changes in the functional organization of the brain. It refers to the brain’s ability to reorganize its functional networks and redistribute tasks among different regions in response to changing demands or damage to specific areas. For example, if a certain brain area becomes damaged due to injury, other healthy areas might take over its functions. 

This process of functional reorganization enables the brain to maintain its overall functionality despite challenges. 

Functional neuroplasticity is closely linked to recovery and adaptation after injuries such as strokes or traumatic brain injuries, as well as during skill acquisition and learning new tasks. It highlights the brain’s remarkable flexibility in redistributing functions to ensure optimal performance.

Neuroplasticity Throughout Our Lifespan

Neuroplasticity is particularly prominent during early brain development, during infancy and childhood

That’s when the brains are highly adaptable and can form a vast number of synaptic connections. This early phase of plasticity allows the brain to build its foundational architecture, establish sensory and motor pathways, and learn fundamental skills like language and basic motor coordination

During adolescence, the brain undergoes another period of heightened plasticity. This is characterized by processes like synaptic pruning, where unused or weaker synapses are eliminated to streamline neural circuits. This pruning process helps refine the brain’s architecture, optimizing it for more complex cognitive functions and higher-order thinking.

Even in adulthood, neuroplasticity persists. While the degree of plasticity might be somewhat reduced compared to early developmental stages–adults continue to learn, adapt, and acquire new skills throughout their lives. 

This is evident in the brain’s ability to reorganize functional networks in response to changing demands, as seen in cases of brain injury or when learning new skills.

Although neuroplasticity might decline with age, especially in terms of the brain’s ability to form new connections, it remains a relevant and dynamic process. The brain can still adapt, learn, and rewire to some extent, even in older adults.

Here are nutritional and lifestyle factors that can enhance neuroplasticity, especially as you get older.

Neuroplasticity Diet

Diet plays a crucial role in supporting neuroplasticity. The nutrients we consume through our diet provide the building blocks for the brain’s structure, communication pathways, and overall function.

Here’s how diet can help enhance neuroplasticity:

1) Omega-3 Fatty Acids  

Omega-3 fatty acids, commonly found in fatty fish like salmon, as well as flaxseeds and walnuts, are known to support brain health.

These fatty acids are essential for maintaining the structure and function of cell membranes in neurons. They also play a role in balancing inflammation and oxidative stress, which can create a more favorable environment for neuroplasticity to occur.

2) Antioxidants

Foods rich in antioxidants, such as berries, dark leafy greens, and colorful fruits, help protect brain cells from oxidative damage. Oxidative stress can negatively impact neuroplasticity, so consuming antioxidants in your diet helps maintain a healthy neural environment.

3) B Vitamins 

B vitamins, including B6, B9 (folate), and B12, are important for brain health and cognitive function. They support the production of neurotransmitters, which are chemicals that allow neurons to communicate. Adequate intake of these vitamins is essential for maintaining optimal neural communication and supporting neuroplasticity.

4) Protein and Amino Acids

Protein-rich foods provide the amino acids necessary for the synthesis of neurotransmitters and other brain molecules. Amino acids like tryptophan, found in sources like turkey and nuts, are precursors to serotonin, a neurotransmitter linked to mood regulation and neuroplasticity.

5) Healthy Fats 

Healthy fats, such as those found in avocados, nuts, and olive oil, are essential for brain cell membrane structure. These fats help neurons communicate efficiently and are crucial for maintaining synaptic plasticity, a key aspect of neuroplasticity.

6) Complex Carbohydrates 

Whole grains, fruits, and vegetables provide complex carbohydrates that serve as the brain’s primary source of energy. A consistent energy supply is essential for maintaining neural function and supporting processes related to neuroplasticity.

7) Hydration 

Staying well-hydrated is essential for brain function. Dehydration can impair cognitive abilities and hinder neuroplasticity processes. Drinking enough water helps maintain the optimal environment for neural communication and plasticity.

8) Phytochemicals

Many plant-based foods contain phytochemicals that may support cognitive health. For example, resveratrol in red grapes and berries has been associated with enhanced learning and memory.

It’s important to adopt a balanced and varied diet to ensure you’re getting a wide range of nutrients that support neuroplasticity. Avoiding excessive sugar, highly processed foods, and unhealthy fats is also essential, as these can contribute to inflammation and hinder brain health.

Lifestyle Tips to Improve Neuroplasticity

There are several other ways to increase neuroplasticity beyond diet, exercise, and supplements. Here are some additional strategies that can contribute to promoting neuroplasticity:

1) Cognitive Engagement  

Cognitive engagement, the active involvement of the brain in various mental tasks and challenges, fosters neuroplasticity. 

When the brain is engaged in learning, problem-solving, or acquiring new skills, it triggers a cascade of neural processes. Neurons fire and form synapses. With repetition and practice, these synapses strengthen, while unused ones weaken or fade away.

Neuroplasticity not only involves structural changes in the brain, such as the growth of new synapses or the strengthening of existing ones, but it also encompasses functional changes, like the brain reallocating resources to support the areas that are most active and relevant to the tasks at hand. Cognitive engagement drives this process. 

As we navigate challenges, the brain adapts by refining its networks, optimizing neural pathways, and expanding its capacity to process information.

Cognitive activities can include:

• Learning a new language
• Solving puzzles
• Doing crosswords
• Playing strategy games

2) Mindfulness and Meditation 

Mindfulness and meditation involve focused attention and awareness, which can lead to changes in brain structure and function. These practices activate the brain’s prefrontal cortex, responsible for higher-order thinking and decision-making, and the right anterior insula.

The anterior insula is a part of our brain that helps us experience emotions and figure out how those emotions impact the way we think and behave.

Regular meditation may enhance gray matter density in the hippocampus, an area involved in memory. This is indicative of neuroplasticity.

Mindfulness improves stress resilience, lowering cortisol levels and reducing chronic stress’s detrimental effects on the brain. Chronic stress can impair neuroplasticity by negatively impacting the hippocampus. Meditation’s stress-mitigating benefits can thus indirectly support neuroplasticity.

Mindfulness also encourages an open, non-judgmental attitude towards experiences, fostering a growth mindset. This mindset can promote a willingness to embrace challenges and learn from failures, both essential components of neuroplasticity.

Additionally, meditation may enhance the brain’s connectivity, improving communication between different regions. Enhanced connectivity supports the formation of new neural pathways and facilitates adaptive responses to novel information and experiences.

3) Social Interaction  

Social interactions play a crucial role in promoting neuroplasticity. Engaging in conversations, debates, and social activities not only feels good but also contributes to better brain health. 

Evidence suggests that socially active individuals may experience fewer memory problems and a reduced risk of dementia. Neuroplasticity, influenced by social engagement, is vital for maintaining cognitive functions like memory, comprehension, communication, and emotional well-being, especially as we age.

4) Novel Experiences 

Experiencing new environments and situations challenges your brain to adapt. Traveling, exploring new places, or even taking a different route to work can stimulate neural connections

5) Aerobic Exercise 

Aerobic activities like running, swimming, and cycling can increase brain-derived neurotrophic factor (BDNF), a protein that supports neurogenesis.

Aerobic exercise also increases neuroplasticity by boosting blood flow and oxygen delivery to the brain. Additionally, exercise can improve the body’s ability to balance inflammation and stress, factors that can hinder neuroplasticity.

Regular exercise promotes a more adaptable and resilient brain, improving cognitive function and supporting learning and memory.

6) Sleep 

High-quality sleep is essential for brain health. 

• During sleep, the brain consolidates and organizes newly acquired information from waking hours. This process, particularly in the deep sleep stages, strengthens synaptic connections, facilitating learning and memory retention .
• Sleep is when the brain eliminates waste products and toxins that accumulate during the day. This housekeeping function supports the brain’s optimal function.
• Deep sleep is associated with an increase in the production of BDNF. 

Therefore, adequate sleep is integral to sustaining neuroplasticity and cognitive vitality.

7) Stress Management 

Effective stress management can increase neuroplasticity by reducing the harmful impact of chronic stress on the brain. 

Chronic stress can damage neurons and hinder synaptic plasticity. Stress management techniques, like mindfulness and relaxation, mitigate stress hormone levels and inflammation, creating a more conducive environment for neural connections to form and adapt, promoting neuroplasticity.

8) Creativity and Artistic Expression

Engaging in creative and artistic expression can increase neuroplasticity by stimulating novel thinking and problem-solving. Painting, drawing, or writing require brain flexibility, encouraging the formation of new connections and strengthening existing ones. This process supports cognitive adaptability, fostering a more agile and open mind .

9) Brain Training Apps

While research on the effectiveness of brain training apps is mixed, some games and apps claim to challenge different cognitive functions, potentially supporting neuroplasticity in older adults. 

These apps engage various brain functions, encouraging the formation and strengthening of neural connections. Regular use of these apps can enhance cognitive skills like promoting neuroplasticity and improved mental agility.

10) Fasting and Intermittent Fasting

Fasting induces the production of neurotrophic factors like BDNF, recognized as a key controller of energy balance. BDNF plays a role in regulating neurogenesis thereby supporting synaptic plasticity, and enhancing the processes of learning and memory.

As we age, the brain’s ability to form new connections may diminish slightly, but it never loses its capacity to adapt and learn. Embracing a lifestyle that fosters ongoing neuroplasticity can help maintain your cognitive vitality and your brain’s full potential. That way, we continue to learn, grow, and thrive throughout our lives.

The brain is an ever-evolving organ, and with the right care and stimulation–it can remain agile and adaptable, defying the limitations often associated with aging, and have optimal function.

Now that you’ve learned about the diet and lifestyle basis for neuroplasticity, in the next article, we’ll share about supplements that can supercharge your neuroplasticity

References

1. Puderbaugh M, Emmady PD. Neuroplasticity. Published online 2023. Accessed September 28, 2023. https://pubmed.ncbi.nlm.nih.gov/32491743/
2. Sharma N, Classen J, Cohen LG. Neural plasticity and its contribution to functional recovery. In: Neurological Rehabilitation. Vol 110. Elsevier; 2013:3-12.
3. Power JD, Schlaggar BL. Neural plasticity across the lifespan. Wiley Interdiscip Rev Dev Biol. 2017;6(1). doi:10.1002/wdev.216
4. Fandakova Y, Hartley CA. Mechanisms of learning and plasticity in childhood and adolescence. Dev Cogn Neurosci. 2020;42(100764):100764. doi:10.1016/j.dcn.2020.100764
5. Laube C, van den Bos W, Fandakova Y. The relationship between pubertal hormones and brain plasticity: Implications for cognitive training in adolescence. Dev Cogn Neurosci. 2020;42(100753):100753. doi:10.1016/j.dcn.2020.100753
6. White EJ, Hutka SA, Williams LJ, Moreno S. Learning, neural plasticity and sensitive periods: implications for language acquisition, music training and transfer across the lifespan. Front Syst Neurosci. 2013;7. doi:10.3389/fnsys.2013.00090
7. Park DC, Bischof GN. The aging mind: neuroplasticity in response to cognitive training. Dialogues Clin Neurosci. 2013;15(1):109-119. doi:10.31887/dcns.2013.15.1/dpark
8. Pauwels L, Chalavi S, Swinnen SP. Aging and brain plasticity. Aging (Albany NY). 2018;10(8):1789-1790. doi:10.18632/aging.101514
9. Phillips C. Lifestyle modulators of neuroplasticity: How physical activity, mental engagement, and diet promote cognitive health during aging. Neural Plast. 2017;2017:1-22. doi:10.1155/2017/3589271
10. Dighriri IM, Alsubaie AM, Hakami FM, et al. Effects of omega-3 polyunsaturated fatty acids on brain functions: A systematic review. Cureus. 2022;14(10). doi:10.7759/cureus.30091
11. Pearson K, RD. How omega-3 fish oil affects your brain and mental health. Healthline. Published December 5, 2017. Accessed September 28, 2023. https://www.healthline.com/nutrition/omega-3-fish-oil-for-brain-health
12. Bertrand E (lizzie). Maximize memory function with a nutrient-rich diet. Mayo Clinic Health System. Published May 30, 2023. Accessed September 28, 2023. https://www.mayoclinichealthsystem.org/hometown-health/speaking-of-health/maximize-memory-function-with-a-nutrient-rich-diet
13. Salim S. Oxidative stress and the central nervous system. J Pharmacol Exp Ther. 2017;360(1):201-205. doi:10.1124/jpet.116.237503
14. Xu H, Wang S, Gao F, Li C. Vitamin B6, B9, and B12 intakes and cognitive performance in elders: National health and nutrition examination survey, 2011–2014. Neuropsychiatr Dis Treat. 2022;18:537-553. doi:10.2147/ndt.s337617
15. Institute of Medicine (US) Committee on Military Nutrition Research. Amino Acid and Protein Requirements: Cognitive Performance, Stress, and Brain Function. National Academies Press; 1999.
16. Puri S, Shaheen M, Grover B. Nutrition and cognitive health: A life course approach. Front Public Health. 2023;11. doi:10.3389/fpubh.2023.1023907
17. Complex carbohydrates. Medlineplus.gov. Accessed September 28, 2023. https://medlineplus.gov/ency/imagepages/19529.htm
18. Adan A. Cognitive performance and dehydration. J Am Coll Nutr. 2012;31(2):71-78. doi:10.1080/07315724.2012.10720011
19. Rajaram S, Jones J, Lee GJ. Plant-based dietary patterns, plant foods, and age-related cognitive decline. Adv Nutr. 2019;10(Suppl 4):S422-S436. doi:10.1093/advances/nmz081
20. Cicero AFG, Ruscica M, Banach M. Resveratrol and cognitive decline: a clinician perspective. Arch Med Sci. 2019;15(4):936-943. doi:10.5114/aoms.2019.85463
21. Namkung H, Kim SH, Sawa A. The insula: An underestimated brain area in clinical neuroscience, psychiatry, and neurology. Trends Neurosci. 2017;40(4):200-207. doi:10.1016/j.tins.2017.02.002
22. Neuroscience News. Unleashing the mind: The neuroscience of meditation and its impact on memory. Neuroscience News. Published June 7, 2023. Accessed September 28, 2023. https://neurosciencenews.com/memory-meditation-23414/
23. Presenter TV. Social interaction and brain health. Hometouch. Published January 4, 2019. Accessed September 28, 2023.
24. Pickersgill JW, Turco CV, Ramdeo K, Rehsi RS, Foglia SD, Nelson AJ. The combined influences of exercise, diet and sleep on neuroplasticity. Front Psychol. 2022;13:831819. doi:10.3389/fpsyg.2022.831819
25. Exercise can boost your memory and thinking skills. Harvard Health. Published February 15, 2021. Accessed September 28, 2023. https://www.health.harvard.edu/mind-and-mood/exercise-can-boost-your-memory-and-thinking-skills
26. Gorgoni M, D’Atri A, Lauri G, Rossini PM, Ferlazzo F, De Gennaro L. Is sleep essential for neural plasticity in humans, and how does it affect motor and cognitive recovery? Neural Plast. 2013;2013:1-13. doi:10.1155/2013/103949
27. Jessen NA, Munk ASF, Lundgaard I, Nedergaard M. The glymphatic system: A beginner’s guide. Neurochem Res. 2015;40(12):2583-2599. doi:10.1007/s11064-015-1581-6
28. Monteiro BC, Monteiro S, Candida M, et al. Relationship between brain-Derived Neurotrofic Factor (bdnf) and sleep on depression: A critical review. Clin Pract Epidemiol Ment Health. 2017;13(1):213-219. doi:10.2174/1745017901713010213
29. ACRM. How the brain is affected by art – rehabilitation medicine. ACRM. Published August 19, 2020. Accessed September 28, 2023. https://acrm.org/rehabilitation-medicine/how-the-brain-is-affected-by-art/
30. Bonnechère B, Klass M, Langley C, Sahakian BJ. Brain training using cognitive apps can improve cognitive performance and processing speed in older adults. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-91867-z
31. Rege S. A simplified guide to the neuroscience of intermittent fasting. Psych Scene Hub. Published February 21, 2023. Accessed September 28, 2023. https://psychscenehub.com/psychinsights/intermittent-fasting-and-brain-health/

Some supplements may support cognitive function and brain health, which could indirectly contribute to neuroplasticity. However, the effects can vary based on factors such as the specific supplement, individual differences, dosage, and overall health.

Certain nutrients and compounds found in supplements for neuroplasticity may play a role in supporting brain health and cognitive function, which can contribute to an environment that supports neuroplasticity.

What Are Neuroplasticity Supplements, Herbs, Nootropics, and How Do They Work?

Omega-3 Fatty Acids 

Omega-3s, found in fish and algae oil supplements, are important for brain health.

They can potentially increase neuroplasticity through several mechanisms:

Enhancing Neuronal Membrane Fluidity 

Omega-3s, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), are essential components of neuronal cell membranes. They help maintain the fluidity and flexibility of these membranes, which is crucial for efficient communication between neurons. Flexible membranes allow for easier transmission of signals and the formation of new connections, supporting neuroplasticity.

Promoting Synaptic Function 

The proper functioning of synapses is essential for learning and memory. Omega-3s may help optimize synaptic transmission and facilitate the strengthening of synaptic connections, which are vital aspects of neuroplasticity.

Supporting Healthy Inflammatory Response

Inflammation in the brain can hinder neuroplasticity by disrupting communication between neurons. Omega-3 fatty acids support healthy inflammatory responses in the nervous system. Therefore,omega-3s create a more conducive environment for neural connections to form and adapt, thereby supporting neuroplasticity.

Increasing Brain-Derived Neurotrophic Factor (BDNF) Levels

BDNF is a protein that promotes the growth, survival, and maintenance of neurons. It is also involved in the formation of new synapses and the adaptation of existing ones, both of which are fundamental processes in neuroplasticity. 

Omega-3 fatty acids, particularly DHA, increase BDNF levels in the brain, facilitating neural connectivity and enhancing the brain’s adaptive capacity.

Modulating Neurotransmitters 

Omega-3s can influence the production and release of neurotransmitters like dopamine, serotonin, and glutamate. These neurotransmitters play central roles in cognitive processes and mood regulation. By helping regulate the balance of neurotransmitters, omega-3s can support overall brain function and emotional well-being, which are integral components of neuroplasticity.

Antioxidants 

Antioxidants can potentially increase neuroplasticity through their ability to neutralize oxidative stress, which can impair the brain’s adaptive capacity. Antioxidants support neuroplasticity in the following ways:

Reducing Oxidative Stress (ROS)

Oxidative stress occurs when there is an imbalance between harmful ROS and the body’s antioxidant defenses. Excessive oxidative stress can damage neurons and their components, including DNA, proteins, and lipids. 

Antioxidants neutralize ROS and help protect neurons from this damage, preserving their function and viability. Healthy neurons are better equipped to engage in neuroplasticity.

 Protecting Mitochondrial Function

Mitochondria are the energy-producing organelles within neurons. Oxidative stress can impair mitochondrial function, leading to energy deficits and decreased neuronal plasticity. Antioxidants can help maintain mitochondrial health by mitigating oxidative damage, ensuring neurons have the energy they need to support neuroplasticity.

Inflammation Modulating Effects 

Unmodulated Chronic inflammation in the brain can hinder neuroplasticity by disrupting the normal functioning of neurons and glial cells. Antioxidants, by modulating inflammation, create a more favorable environment for neural plasticity. They can modulate immune responses, supporting overall brain health.

 Promoting BDNF Production

As previously mentioned, BDNF is a protein that plays a crucial role in neuroplasticity. Some antioxidants, such as flavonoids found in certain fruits and vegetables, increase the production of BDNF. Elevated BDNF levels facilitate the formation of new synapses and strengthen existing ones, which are essential aspects of neuroplasticity.

B Vitamins 

B vitamins play an important role in brain health and can support neuroplasticity through several mechanisms:

 Neurotransmitter Production 

B vitamins, particularly B6 (pyridoxine), B9 (folate), and B12 (cobalamin), are essential for the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine. Ensuring an adequate supply of these B vitamins helps maintain neurotransmitter balance, which is important for neuroplasticity.

 Homocysteine Regulation 

Elevated levels of homocysteine, an amino acid, are associated with an increased risk of cognitive decline. B vitamins, specifically folate, B6, and B12, help regulate homocysteine levels in the body. B vitamin supplementation may help reduce the risk of cognitive impairment and support overall brain health, including neuroplasticity.

 DNA Methylation and Synaptic Plasticity

DNA methylation is an epigenetic process that can influence gene expression. B vitamins, particularly folate, play a role in DNA methylation, which can affect the expression of genes involved in synaptic plasticity. Proper methylation patterns are necessary for the formation and strengthening of synaptic connections, a fundamental process in neuroplasticity.

 Protection Against Oxidative Stress 

B vitamins, including niacin (B3) and riboflavin (B2), are involved in your body’s antioxidant defenses. Antioxidants help protect neurons from oxidative stress, which can damage cell membranes, proteins, and DNA. By reducing oxidative stress, B vitamins support the health and function of neurons and facilitate neuroplasticity.

 Mood Regulation 

B vitamins are known to play a role in mood regulation, and mood is closely linked to cognitive function and neuroplasticity. For example, B6 is involved in the production of serotonin, a mood-enhancing neurotransmitter. Balancing mood can indirectly support cognitive processes and neuroplasticity.

A balanced diet with foods rich in B vitamins, such as leafy greens, legumes, nuts, and fortified cereals, can provide the necessary nutrients to support brain health and neuroplasticity. However, in cases of deficiency or certain medical conditions, B vitamin supplementation may be recommended under the guidance of a healthcare professional. 

Lion’s Mane Mushroom (Hericium erinaceus)

Lion’s mane mushroom (Hericium erinaceus) is a natural dietary supplement that has gained attention for its potential to support neuroplasticity and overall brain health. While the exact mechanisms of how lion’s mane mushroom influences neuroplasticity are still being researched, there are several ways it may contribute to this process:

 Nerve Growth Factor (NGF) and pro-BDNF Stimulation 

Lion’s Mane Mushroom contains compounds known as hericenones and erinacines, which have been shown in some studies to stimulate the production of nerve growth factor (NGF). NGF is a protein essential for the growth, maintenance, and survival of neurons. 

By promoting NGF production, Lion’s Mane Mushroom may facilitate the growth of new neurites (extensions of nerve cells) and the formation of new synaptic connections, which are key aspects of neuroplasticity.

Lion’s Mane Mushroom supplements increase levels of pro-BDNF, which is a precursor to BDNF. Pro-BDNF is synthesized and released by neurons and is involved in synaptic pruning which is an important process of neuroplasticity. 

 Enhanced Myelination 

Myelin is the protective sheath that covers nerve fibers and enhances the efficiency of signal transmission between neurons. Lion’s Mane Mushroom may support myelination by promoting the growth and differentiation of oligodendrocytes, the cells responsible for myelin production. 

Improved myelination can lead to faster and more efficient communication between neurons, potentially enhancing neuroplasticity.

 Antioxidant Properties 

Lion’s Mane Mushroom is rich in antioxidants, which help combat oxidative stress and reduce damage to neurons caused by free radicals. Oxidative stress can impair neuronal function and hinder neuroplasticity. By reducing oxidative stress, Lion’s Mane Mushroom may create a more favorable environment for synaptic plasticity and neural adaptation.

 Inflammation-Balancing Effects

Lion’s Mane Mushroom has immune-balancing properties, which may help promote a healthy inflammatory response and thus a healthier environment for synaptic remodeling and plasticity.

 Improved Cognitive Function 

Some studies suggest that lion’s mane mushroom supplementation can lead to improved cognitive function, including memory and learning. Enhanced cognitive abilities can indirectly support neuroplasticity by facilitating the acquisition of new information and the formation of new neural connections.

While there is promising research on the potential benefits of Lion’s Mane Mushroom for neuroplasticity, more studies are needed to fully understand its mechanisms and effects. 

Individual responses to Lion’s Mane Mushroom may vary, and its use should be approached with caution, especially if you have any underlying medical conditions or are taking medications. As with any dietary supplement, it’s advisable to consult with a healthcare professional before incorporating lion’s mane mushroom into your routine.

Caffeine

Caffeine is a stimulant that primarily affects the central nervous system, and while it is more commonly associated with increasing alertness and concentration, it can also have some indirect effects on neuroplasticity.

 Enhanced Cognitive Function

Although there is no clear consensus, some studies suggest that caffeine can temporarily improve cognitive function, including attention, memory, and learning. 

By increasing alertness and mitigating the sensation of fatigue, caffeine may help individuals engage more effectively in cognitive tasks that require neuroplasticity, such as learning new information or adapting to changing circumstances. This enhanced cognitive function can indirectly support neuroplasticity by facilitating the acquisition and processing of new information.

 Stimulation of Neurotransmitter Release 

Caffeine stimulates the release of certain neurotransmitters, including dopamine and norepinephrine, in the brain. These neurotransmitters play roles in mood regulation, attention, and arousal. Increased neurotransmitter activity can enhance alertness and focus, potentially aiding in the engagement of cognitive processes associated with neuroplasticity.

 Improved Synaptic Transmission 

Caffeine can enhance synaptic transmission, the process by which signals are transmitted between neurons at synapses. It can increase the release of neurotransmitters like glutamate, which is crucial for synaptic plasticity and learning. 

By promoting more efficient signaling between neurons, caffeine can indirectly support the strengthening and formation of neural connections, essential aspects of neuroplasticity.

 Neuroprotective Effects 

Some studies suggest that caffeine has neuroprotective properties, which means it may help protect neurons from damage caused by factors like oxidative stress and neuroinflammation. By preserving the health of neurons, caffeine can create a more conducive environment for neuroplasticity to occur.

By blocking adenosine receptors, caffeine enhances alertness, potentially influencing neural activity and learning. This heightened neuronal firing, along with potential BDNF elevation, might foster an environment conducive to neuroplasticity. However, individual responses to caffeine vary, and excessive intake can lead to negative effects.

The caffeine’s effect on neuroplasticity can vary among individuals and depend on factors such as the dose of caffeine consumed and an individual’s tolerance to caffeine. 

While moderate caffeine consumption may have some potential cognitive benefits, excessive caffeine intake can lead to side effects, including anxiety, jitteriness, and disrupted sleep, which can ultimately impair cognitive function and neuroplasticity.

Additionally, the long-term effects of chronic caffeine use on neuroplasticity are still an active area of research, and more studies are needed to fully understand the relationship between caffeine and brain plasticity. It’s advisable to consume caffeine in moderation and be mindful of its potential side effects, especially if you have underlying medical conditions or are sensitive to caffeine.

Bacopa Monnieri

Bacopa monnieri, commonly known as Brahmi, is an herb used in traditional medicine, particularly in Ayurveda, that is believed to have several cognitive-enhancing properties, including the potential to increase neuroplasticity. 

Although no research has directly shown that Bacopa monnieri directly causes neuroplasticity, here are some ways Bacopa monnieri may influence neuroplasticity:

 Enhanced Synaptic Transmission

Bacopa monnieri is thought to enhance synaptic transmission, which is the process by which neurons communicate at synapses. It may increase the release of neurotransmitters like acetylcholine, which is important for learning and memory. 

Improved synaptic transmission can facilitate the strengthening and formation of neural connections, a key aspect of neuroplasticity.

 Neuroprotective Effects

Bacopa monnieri is rich in antioxidants, which help protect neurons from oxidative stress and damage caused by free radicals. By preserving the health of neurons, Bacopa monnieri can create a more conducive environment for neuroplasticity to occur.

 Modulation of Neurotransmitters 

Bacopa monnieri may influence the levels and activity of various neurotransmitters, including serotonin, dopamine, and GABA (gamma-aminobutyric acid). Modulating neurotransmitter activity can indirectly support neuroplasticity by enhancing cognitive function and emotional well-being.

 Stress Reduction 

Chronic stress can impair cognitive function and hinder neuroplasticity. Bacopa monnieri may promote calmness and enhance mood. By mitigating stress, it can create a more favorable environment for the brain to engage in neuroplasticity processes.

 Enhanced Memory Consolidation

Bacopa monnieri may help with improved memory retention and consolidation. The formation of long-term memories involves synaptic plasticity, and enhancing memory processes can indirectly support neuroplasticity.

 Neurotrophic Factor Modulation

Some research suggests that Bacopa monnieri may influence the expression of brain-derived neurotrophic factor (BDNF), a protein critical for the growth, survival, and adaptability of neurons. Elevated BDNF levels facilitate the formation of new synapses and the strengthening of existing ones, fundamental processes in neuroplasticity.

Supplements, herbs, and nootropics show promise in enhancing neuroplasticity, which is crucial for brain adaptability and cognitive health. Omega-3 fatty acids, antioxidants, B vitamins, Lion’s Mane Mushroom, and caffeine can potentially support neuroplasticity through various mechanisms. 

These compounds aid in maintaining neuronal health, promoting synaptic function, balancing inflammation, and enhancing neurotransmitter activity. 

While these supplements offer exciting potential, individual responses vary, necessitating consultation with healthcare professionals, especially for those with underlying health conditions. A well-balanced diet rich in these nutrients can also contribute to brain health and cognitive adaptability. 

These supplements offer a promising avenue for individuals seeking to improve cognitive function and overall well-being.

References:

1. DiNicolantonio JJ, O’Keefe JH. The importance of marine omega-3s for brain development and the prevention and treatment of behavior, mood, and other brain disorders. Nutrients. 2020;12(8):2333. doi:10.3390/nu1208233
2. Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568-578. doi:10.1038/nrn2421
3. Layé S, Nadjar A, Joffre C, Bazinet RP. Anti-inflammatory effects of omega-3 fatty acids in the brain: Physiological mechanisms and relevance to pharmacology. Pharmacol Rev. 2018;70(1):12-38. doi:10.1124/pr.117.014092
4. Liao L, Pilotte J, Xu T, et al. BDNF induces widespread changes in synaptic protein content and up-regulates components of the translation machinery: An analysis using high-throughput proteomics. J Proteome Res. 2007;6(3):1059-1071. doi:10.1021/pr060358f
5. Healy-Stoffel M, Levant B. N-3 (omega-3) fatty acids: Effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets. 2018;17(3):216-232. doi:10.2174/1871527317666180412153612
6. Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev. 2017;2017:1-13. doi:10.1155/2017/8416763
7. Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research. 2013;8(21):2003. doi:10.3969/j.issn.1673-5374.2013.21.009
8. Mattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008;60(5):748-766. doi:10.1016/j.neuron.2008.10.010
9. DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(S2):136-153. doi:10.1111/jnc.13607
10. Pisoschi AM, Pop A, Iordache F, et al. Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Eur J Med Chem. 2022;232(114175):114175. doi:10.1016/j.ejmech.2022.114175
11. Cichon N, Saluk-Bijak J, Gorniak L, Przyslo L, Bijak M. Flavonoids as a natural enhancer of neuroplasticity—an overview of the mechanism of neurorestorative action. Antioxidants (Basel). 2020;9(11):1035. doi:10.3390/antiox9111035
12. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015;6(6):1164-1178. doi:10.5114/aoms.2015.56342
13. Calderón-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther. 2020;26(1):5-13. doi:10.1111/cns.13207
14. Garcia A. Homocysteine and cognitive function in elderly people. CMAJ. 2004;171(8):897-904. doi:10.1503/cmaj.1031586
15. 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
16. Kennedy D. B vitamins and the brain: Mechanisms, dose and efficacy—A review. Nutrients. 2016;8(2):68. doi:10.3390/nu8020068
17. Lai PL, Naidu M, Sabaratnam V, et al. Neurotrophic properties of the lion’s mane medicinal mushroom, Hericium erinaceus (higher basidiomycetes) from Malaysia. Int J Med Mushrooms. 2013;15(6):539-554. doi:10.1615/intjmedmushr.v15.i6.30
18. Vigna L, Morelli F, Agnelli GM, et al. Hericium erinaceus improves mood and sleep disorders in patients affected by overweight or obesity: Could circulating pro-BDNF and BDNF be potential biomarkers? Evid Based Complement Alternat Med. 2019;2019:1-12. doi:10.1155/2019/7861297
19. Kolotushkina EV, Moldavan MG, Voronin KY, Skibo GG. The influence of Hericium erinaceus extract on myelination process in vitro. Fìzìol ž. 2003;49(1).
20. Ghosh S, Nandi S, Banerjee A, Sarkar S, Chakraborty N, Acharya K. Prospecting medicinal properties of Lion’s mane mushroom. J Food Biochem. 2021;45(8). doi:10.1111/jfbc.13833
21. Mori K, Ouchi K, Hirasawa N. The anti-inflammatory effects of lion’s mane culinary-medicinal mushroom, Hericium erinaceus (higher basidiomycetes) in a coculture system of 3T3-L1 adipocytes and RAW264 macrophages. Int J Med Mushrooms. 2015;17(7):609-618. doi:10.1615/intjmedmushrooms.v17.i7.10
22. Rossi P, Cesaroni V, Brandalise F, et al. Dietary supplementation of lion’s mane medicinal mushroom, Hericium erinaceus (Agaricomycetes), and spatial memory in wild-type mice. Int J Med Mushrooms. 2018;20(5):485-494. doi:10.1615/intjmedmushrooms.2018026241
23. McLellan TM, Caldwell JA, Lieberman HR. A review of caffeine’s effects on cognitive, physical and occupational performance. Neurosci Biobehav Rev. 2016;71:294-312. doi:10.1016/j.neubiorev.2016.09.001
24. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev. 1992;17(2):139-170. doi:10.1016/0165-0173(92)90012-b
25. Yoshimura H. The potential of caffeine for functional modification from cortical synapses to neuron networks in the brain. Curr Neuropharmacol. 2005;3(4):309-316. doi:10.2174/157015905774322543
26. Wasim S, Kukkar V, Awad VM, Sakhamuru S, Malik BH. Neuroprotective and neurodegenerative aspects of coffee and its active ingredients in view of scientific literature. Cureus. 2020;12(8). doi:10.7759/cureus.9578
27. Walker EA, Pellegrini MV. Bacopa Monnieri. StatPearls Publishing; 2023.
28. Brown W. Bacopa Monnieri Research Analysis. Published online 2023. Accessed September 27, 2023.
29. Keegan AP, Stough C, Paris D, et al. Bacopa monnieri supplementation has no effect on serum brain-derived neurotrophic factor levels but beneficially modulates nuclear factor kappa B and cyclic AMP response element-binding protein levels in healthy elderly subjects. Journal of Clinical and Translational Research. 2023;9(1):50.
30. Simpson T, Pase M, Stough C. Bacopa monnierias an antioxidant therapy to reduce oxidative stress in the aging brain. Evid Based Complement Alternat Med. 2015;2015:1-9. doi:10.1155/2015/615384
31. Rajan KE, Preethi J, Singh HK. Molecular and Functional Characterization ofBacopa monniera: A Retrospective Review. Evid Based Complement Alternat Med. 2015;2015:1-12. doi:10.1155/2015/945217
32. Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: A randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008;14(6):707-713. doi:10.1089/acm.2008.0018

Neurotransmitter dominance is an active area of research since both genetics and environment shape your personality. The only way to directly measure neurotransmitters involves cutting the skull open, so none of the dominances come from direct measurements of neurotransmitter levels in humans. 

Instead, most of these links are indirectly deduced from what we know about how these neurotransmitters affect our thoughts and actions, and subsequently supported by genetic studies. In this article, we’ll cover neurotransmitter dominances as described by Drs. Helen Fisher and Eric Braverman. 

What Are Neurotransmitter Dominances?

The human brain is one of the most marvelous and complex organs in your body with intricate neuronal connections. Neurotransmitters are molecules that facilitate the communications between neurons. The neurotransmitters play a crucial role in regulating various bodily functions including mood, behavior, and cognition. 

Neurotransmitter dominance refers to:

1. The individual tendency to have high or low levels of neurotransmitters in the brain
2. How these variations can impact an individual’s personality and behavior. 

Dr. Helen Fisher is an anthropologist, whereas Dr. Eric Braverman is a medical doctor. They independently studied neurotransmitters and how they may be linked to aspects of a person’s behavior and personality traits. They believe neurotransmitter dominances can significantly impact an individual’s personality traits and tendencies.

According to Dr. Fisher, individuals can have different styles of thinking, she categorizes them as explorers, builders, directors, and negotiators. These correspond to dominances in dopamine, serotonin, testosterone, and estrogen, respectively. She believes each of those categories is linked to the dominance of a particular neurotransmitter. For example, dopamine-oriented people are considered “explorers” and more novelty-seeking.

Whereas, Dr. Braverman categorizes people into acetylcholine, dopamine, serotonin, and GABA types. Each dominant neurotransmitter is associated with certain personality traits and behaviors.

Can You Have More Than One Neurotransmitter Dominances?

Yes, individuals can have more than one neurotransmitter dominance. People can score high in two neurotransmitters on the Braverman Personality Type Assessment and so they can be categorized as a mix of two, for example, one can be an Explorer-Director or Builder-Negotiator.

Now, let’s look into different neurotransmitter dominances.

Braverman Acetylcholine Dominance Personality

Acetylcholine is a key neurotransmitter in the brain responsible for memory, creativity, movement, and more. Dr. Braverman refers to acetylcholine-oriented people as the “creative acetylcholine nature”. 

Cognitive Traits of acetylcholine dominances include being:

• Highly creative and open to new ideas
• Quick thinkers who consider others’ perspectives important. 
• Devoted to optimizing things regardless of the effort required
• High inflexibility, creativity, and spontaneity, embracing anything new and exciting. 

When their acetylcholine nature is in balance, they become intuitive and innovative, finding pleasure in words, ideas, and communication..

They excel in roles such as:

• Counselors
• Mediators
• Think tank members
• Yoga and meditation instructors
• Religious leaders
• Public service positions
• Artistic
• Writing
• Advertising
• Acting professions 

In terms of personality, acetylcholine-dominant people are:

1. Extremely social and charismatic. 
2. Relish meeting new people and effortlessly create friendships. 
3. Perceived by others as authentic and grounded, finding their charm endearing. 
4. Natural at forming relationships, and they invest time and energy to nurture meaningful relationships. 
5. Optimistic and see the potential in people. 
6. Attentive to children’s needs and romantic gestures toward their partners.
7. Empathetic and avoid hurting other people.
8. Adventurous and welcome new experiences. Not surprisingly, they love to travel. Their thirst for knowledge makes them interesting to others and fun to talk to.

Braverman and Fisher’s Dopamine Personality

Dopamine is a very important neurotransmitter in the brain and is associated with pleasure, reward, motivation, and goal-directed behavior. People with a dominant dopamine personality may be:

• Adventurous
• Risk-takers who seek new and exciting things
• Goal-oriented and may even display impulsiveness
  

 Dr. Fisher calls dopamine-dominant people “explorers”.

According to Dr. Fisher, these explorers are known for their high energy, optimism, and abundant generation of ideas. Notable examples of dopamine-oriented thinkers cited by Fisher include:

1. Barack Obama

2. Gloria Steinem

3. Peter Thiel, co-founder of PayPal.

Despite their diverse backgrounds and contributions, they share a common biological temperament driven by dopamine.

In a work environment, explorers offer numerous advantages: 

• They are quick thinkers, always on the lookout for opportunities, and excel in handling crisis situations. 
• Their ability to think fast and seize opportunities makes them valuable assets in the workplace, where their adaptability and creativity can drive success. 
• Additionally, their aptitude for dealing with crises efficiently ensures smooth problem-solving and effective decision-making.

According to Dr. Braverman, dopamine-oriented individuals are full of energy. They are able to dedicate all their focus to one task and execute it well. They are likely to be:

• Strong-willed individuals who know exactly what they want and how to achieve it. 
• Quick thinkers and self-confident in their actions.
• Very rationale, making them more comfortable dealing with facts and figures than emotions.
• Good at critical self-assessment but might not handle criticism from others well. 
• Focused on the task at hand, they take pride in their achievements
• Tireless with more heightened alertness, so they may need less sleep than others.
• Not very sensitive to emotions and may prioritize reason over feelings.
• In relationships, they might appear distant from their children, and the stability of their marriage may hinge on the loyalty and goodwill of their spouse.

Strategic thinking, masterminding, inventing, problem-solving, envisioning, and pragmatism are areas that excite them, and they perform well under stress.  Although this doesn’t exclude them from other careers, dopamine-dominant individuals will often be:

•  Doctors
•  Scientists
•  Researchers
•  Inventors
•  Engineers
•  Generals
•  Architects

According to Dr. Braverman, dopamine-dominant individuals enjoy activities such as:

• Playing chess
• Listening to audiobooks
• Challenging crossword puzzles

Braverman and Fisher’s Serotonin personality

Serotonin is a neurotransmitter that plays a crucial role in regulating mood, emotions, and social behavior. It is often associated with feelings of well-being, happiness, and contentment. Low serotonin levels can lead to mood disorders and lowered satisfaction in life.

Serotonin-dominant individuals tend to be emotionally stable, empathic, and seek contentment and social harmony. Dr. Fisher calls them “builders”. Dr. Braverman calls it the “playful serotonin nature.”

These individuals exhibit the following characteristics:

• Cautious and collected demeanor, showing composure even in demanding situations.
• Effective and high-performing under pressure, highlighting their resilience and adaptability. 
• Great attention to detail, meticulous, and bring ideas to fruition with precision. 
• Very cheerful and uplift those around them.
• Positive outlook and optimism create a welcoming and encouraging atmosphere in both personal and professional settings .

Dr. Fisher believes that if an “explorer” is presented with an idea, it would be the serotonin-oriented “builder” who would come up with a plan to execute it. 

Dr. Braverman believes individuals with the playful serotonin nature may have these characteristics:

• The ability to live in the present moment, being realistic and highly responsive to sensory input, while occasionally displaying impulsiveness.
• Engaging in activities for the sheer love of the experience, rather than focusing on the end result, this brings them a sense of accomplishment.
• Embracing change, readily switching tasks, and seeking innovative approaches to repetitive ones. 
• Trying new foods, exploring new hobbies, and planning different vacations each year are all part of their adventurous nature.
• In relationships, passionate but value freedom and independence.
• Their impulsivity and love for new experiences can lead to many varied friendships, although they may not always be deep-rooted.
• A strong sense of loyalty binds them to coworkers, friends, and family, making them appreciated for their practical approach and ability to make the best of any situation.
• Maintaining order and routine might not align with their nature, occasionally impacting their closest relationships .

In balanced states, individuals with a serotonin nature are receptive to stimuli, physically coordinated, and resourceful. Challenges and setbacks do not deter them, as they find excitement in problem-solving. Their serotonin-dominant disposition makes them well-suited for professions requiring:

1. Motor skills
2.  Hand-eye coordination
3.  Flexibility, and crisis management .

According to Dr. Braverman, serotonin-dominant individuals enjoy activities that offer them lots of excitement such as:

• Parties and celebrations
• Mountain climbing
• Skydiving
  

Braverman GABA Dominant Personality 

Gamma-Aminobutyric Acid (GABA) is a neurotransmitter that functions as an inhibitory neurotransmitter in the brain. It plays a crucial role in regulating anxiety, stress, and overall neuronal excitability. GABA has a calming and relaxing effect on the nervous system.

Individuals who are GABA dominant tend to be:

• Calm amidst chaos, naturally embodying traits of objectivity
• Emotionally stable and tend to not worry too much
• Level-headed
• Punctual
• Practical
• Confident 
• Disciplined and organized

Dr. Braverman calls them as having the “stable GABA nature” . 

GABA-dominant individuals often gravitate toward careers such as:

• Administrators
• Accountants
• Security officers
• Nurses
• Medical technicians
• Air-traffic controllers
• News reporters
• EMTs
• Meeting planners
• Bus drivers
• Homemakers

In any job or group setting, the GABA-natured person serves as a grounding force, remaining focused on the task at hand and usually deferring to the majority. They excel as team players.

The GABA-natured person tends to enjoy:

• Both group activities and intimate connections. 
• Making others comfortable 
• A fulfilling long-term marriage 
• Engaging in religious worship and activities
• History books and biographies
• Collecting memorabilia and creating scrapbooks.

Fisher’s Testosterone Personality

Testosterone is a hormone and not a neurotransmitter. Although mostly regarded as a male hormone, females also have it. 

Testosterone plays an important role in many physiological processes, including cognition, in both men and women. It is often associated with traits such as assertiveness, competitiveness, and sexual desire .

Termed as “directors” by Dr. Fisher, testosterone personality type people demonstrate:

• Remarkable analytical and logical abilities
• Proficiency in music and mathematics as they possess a keen understanding of rule-based systems
• Competitiveness
• Goal-orientedness
• Decisiveness

Innovative thinkers, like Apple founder Steve Jobs and politician Hillary Clinton, fall into this category. With their visionary approach, directors lead transformative changes, especially in technology, science, and other rule-bound domains. 

Their ability to conceptualize and implement groundbreaking ideas propels them to the forefront of progress, shaping and influencing the world in significant ways.

Fisher’s Estrogen Personality

Like testosterone, estrogen is also a hormone. It is present in both males and females albeit in smaller amounts in males. Beyond its roles in the development and functioning of the female reproductive system, estrogen also has various effects on the brain and body.  

Estrogen can in fact modulate neurotransmitter systems in the brain including serotonin, dopamine, and norepinephrine . Therefore, estrogen can influence mood, cognition, and behaviors in both genders.

Dr. Fisher refers to estrogen-dominant individuals as “negotiators”.  They approach challenging situations by carefully considering all options and demonstrating diplomatic intelligence. They also excel in team-building and conflict resolution, often pursuing careers in writing and public relations . 

Their adeptness in navigating complex situations, fostering collaboration, and utilizing their communication skills has contributed to their success in various fields. Lastly, negotiators’ ability to find common ground and harmonize differing perspectives makes them valuable assets in achieving mutually beneficial outcomes .

Prominent figures such as Charles Darwin, Oprah Winfrey, and Bill Clinton exemplify the negotiator type. 

Is There Scientific Evidence to These Categorizations?

While the concept of neurotransmitter dominance personality types is intriguing, it is important to consider the scientific evidence supporting these categorizations. 

The link between neurotransmitters and personality is a complex area of research, involving both genetics and environmental factors .

In a study published in Nature Communications, researchers investigated the relationship between genetic variations related to neurotransmitter function and personality traits. They found two key components:

1. Specific genetic variations related to neurotransmitter function were associated with distinct personality traits. For instance, variations in the DRD2 gene, which is involved in dopamine signaling, were linked to traits like novelty-seeking and impulsivity. 

2. Genetic variations in the 5-HTTLPR gene, which affects serotonin signaling, were associated with emotional stability and empathy.

Another study identified specific single nucleotide polymorphisms (SNPs) associated with cognitive abilities and personality traits. Their findings suggest that:

1. Genetic variations in the BDNF gene, which is involved in neuroplasticity and acetylcholine signaling, were linked to cognitive flexibility and learning.

2. Similarly, variations in the COMT gene, involved in dopamine, epinephrine, and norepinephrine signaling, were associated with cognitive performance and impulsivity.

Although the evidence supporting these categorizations is growing, personalities and cognitive functions are influenced by both genetic variations and environmental factors.

What to Do With Your Neurotransmitter Dominance and Tendencies?

Understanding one’s neurotransmitter dominance can have significant implications for personalized approaches to cognitive support, fitness, and nutrition. 

Fitness and nutrition practitioners like Charles Poliquin have advocated training and nutrition regimens based on an individual’s neurotransmitter dominance .

One study found that participants who underwent personalized brain training reported significant improvements in cognitive functions, including memory and attention. The researchers also noted positive changes in mood and overall well-being in individuals who followed tailored cognitive support regimens based on their neurotransmitter dominance . 

Understanding your neurotransmitter dominance can empower you to make informed decisions about:

1. Cognitive support
2. Fitness
3. Nutrition
   

For instance, individuals with GABA dominance, known for their calm and relaxed demeanor, may benefit from mindfulness practices and stress-reducing activities. 

On the other hand, those with dopamine dominance, who are driven by novelty-seeking and risk-taking, might thrive in challenging and adventurous environments. By living according to your tendencies, you can enhance your overall well-being and cognitive performance. 

As research in this field continues to evolve, personalized approaches to brain health and cognitive support will likely play an increasingly prominent role in optimizing human potential.

References:

1. Sheffler ZM, Reddy V, Pillarisetty LS. Physiology, Neurotransmitters. Published online 2023. Accessed August 24, 2023. https://pubmed.ncbi.nlm.nih.gov/30969716/
2. Rosicky BM, Hall EE. Using personality and temperament to predict exercise behavior: A pilot study of the Braverman Nature Assessment. International Journal of Exercise Science. 2022;15(5):341.
3. LJ. Helen Fisher offers insights into what drives personality in Elon lecture. Today at Elon. Accessed August 24, 2023. https://www.elon.edu/u/news/2018/10/26/helen-fisher-offers-insights-into-what-drives-personality-in-elon-lecture/
4. Drtimkelly.net. Accessed August 24, 2023. https://www.drtimkelly.net/fileupload/bravermantestresultsinfo.pdf
5. Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. The role of dopamine and its dysfunction as a consequence of oxidative stress. Oxid Med Cell Longev. 2016;2016:1-13. doi:10.1155/2016/9730467
6. Braverman test neurotransmitter profile. Bravermantest.net. Published August 31, 2021. Accessed August 24, 2023. https://bravermantest.net/
7. Wu C, Sun D. GABA receptors in brain development, function, and injury. Metab Brain Dis. 2015;30(2):367-379. doi:10.1007/s11011-014-9560-1
8. Delgado BJ, Lopez-Ojeda W. Estrogen. Published online 2023. Accessed August 24, 2023. https://pubmed.ncbi.nlm.nih.gov/30855848/
9. Thys B, Grunst AS, Staes N, Pinxten R, Eens M, Grunst ML. The serotonin transporter gene and female personality variation in a free-living passerine. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-88225-4
10. Fischer R, Lee A, Verzijden MN. Dopamine genes are linked to Extraversion and Neuroticism personality traits, but only in demanding climates. Sci Rep. 2018;8(1):1-10. doi:10.1038/s41598-017-18784-y
11. Schlick JP. What type of athlete are you? (this test will tell you.). The Inertia. Published August 28, 2015. Accessed August 24, 2023. https://www.theinertia.com/surf/the-five-elements-of-athlete-its-all-about-neurotransmitters/

Mr. Noots and his team have been meticulously learning from his client feedback for as long as he’s been creating personalized nootropics. Early in his career, he noticed that some clients that were aging were not responding to the nootropics.

Once he tried introducing pro-hormones such as DHEA and pregnenolone, his clients started to reap significant cognitive benefits from the nootropics. In other words, it’s essential for the brain to have these things to function well:

• Hormones
• Oxygen
• Sleep
• Nutrition

Even the best nootropics cannot replace these other needs.

In this article, we’ll cover the fascinating roles of sex steroid hormones in your brain and cognitive function. Then, we’ll discuss whether you’re the best candidate to reap significant benefits from sex hormone support with our DHeA/DHSheA formulas. 

Sex Steroid Hormones And Your Brain

Neurotransmitters are not the only power players in the brain—sex hormones strongly control your brain function and maintenance. We know this because there are numerous sex hormone receptors throughout the brain in both males and females. 

Also, the hypothalamus and pituitary in your brain control your sex hormone production. In short, your brain has a two-way relationship with your sex hormones. This explains steep declines in cognitive health (and often mental health) in some women approaching menopause and some men with low testosterone.

How Your Brain Controls Your Sex Hormones

Sex hormones are part of the hypothalamus-pituitary-gonadal (HPG) axis. The hypothalamus and pituitary are two small glands that lie deep in the brain. Whereas your gonads refer to ovaries in females and testicles in males. Your brain controls sex hormone levels through the following:

1. The hypothalamus releases gonadotropin-releasing hormone (GnRH). 
2. GnRH then stimulates the anterior pituitary gland to release gonadotropins (luteinizing hormone, LH and follicle-stimulating hormones, FSH) into the bloodstream. 
3. LH and FSH travel to the gonads and stimulate the release of sex steroid hormones, including estrogen, progesterone, and testosterone.

The adrenal glands also produce a small amount of sex hormones in both genders.

How Sex Hormones Influence Your Mood And Cognitive Function

Sex hormones strongly influence cognitive functioning, specifically enhancing learning and memory. During development, all the way to your late 20s, sex hormones also influence your brain development.

Aside from classic brain functions, your brain also regulates many essential functions, including:

• Breathing
• Digestion and gut movement
• Body temperature
• Blood pressure

Not surprisingly, your sex hormones can also affect many of these bodily functions through your brain.

What Happens In Women’s Brains As They Go Through Menopause

During menopause, sex hormones in a woman’s body fluctuate greatly. In particular, the levels of estrogen and progesterone fall, causing LH and FSH to go up. This loss of sex hormones is associated with an increased risk for cognitive decline. 

In fact, women who have menopause at an older age or who remain reproductive for a longer period of time have higher cognitive performance, and their cognitive decline is delayed. 

A six-year study of 1,903 perimenopausal women explored the relationship between cognitive performance changes and menopause symptoms of depression and anxiety. Participants took three tests:

• Processing speed
• Verbal memory
• Working memory

Those reporting higher symptoms of depression and anxiety had slower cognitive processing speeds than those who did not demonstrate menopausal symptoms.

A meta-analysis of studies examined cognition and depression during different stages of the menopausal transition. The results showed that postmenopausal women had lower performance on tests of phonemic verbal fluency and delayed verbal memory compared to perimenopausal women.

Additionally, both perimenopausal and postmenopausal women were more likely to experience significant mood issues than premenopausal women.

So, what’s happening in the brain? A study of 182 women ages 40-65 provided some insight. They found three major neurological changes:

1. Brain Anatomy: Brain structure can be affected, particularly in cortical and subcortical regions. Women in the post-menopausal and perimenopausal groups show lower gray matter volume in certain areas. However, post-menopausal women experience selective recovery in the precuneus. The precuneus is important for social processes, memory, and information integration.

2. White Matter Volume (WMV): Another change is in the white matter, which is like the wiring that helps different brain areas communicate. Women going through menopause may experience a loss of white matter compared to men of the same age. However, despite this loss, the remaining white matter becomes more efficient in how it works. It’s like a smaller but smarter wiring system in the brain. This helps the brain to work better even with less white matter.

3. Brain Energetics: The way the brain gets its energy can also change. In post and perimenopause groups, certain parts of the brain use less glucose, the brain’s main energy source. 

Some clinical studies suggest that fats in the white matter may be broken down into ketones for energy, which may contribute to the loss of brain tissues during menopause. However, the overall rate of glucose use in the brain stays relatively stable after menopause, which means the brain adjusts to a new way of getting energy after a long time without estrogen.

In addition, there is more blood flow and energy molecule called ATP in certain brain regions, specifically in the areas related to thinking and remembering things. More blood flow and ATP are linked to better overall brain function. These changes suggest that the brain adapts to alternative energy sources when less glucose is available. 

What Happens In Men’s Brains As They Age

Like women, men also experience a decline in sex hormones as they age. Women undergo menopause and have a steep hormonal decline, while men experience a more gradual and progressive decline, especially in testosterone and dehydroepiandrosterone (DHEA). 

While everyone’s brain shrinks with age and the brain’s metabolism slows down, these changes seem to happen faster in men. On average, the male brain is functionally three years older than the female brain throughout young adult land adulthood.

A study compared age-matched brain images of 53 males and 50 females. Researchers found that the male hippocampus was consistently smaller than females. Men also had a significant decrease in the size of the caudate putamen (which controls motor function) while women did not.

Hormones Involved In Brain Changes

Estrogen 

Estrogen receptors are widely distributed throughout the brain.  There are two major subtypes:

1. Alpha estrogen receptors
2. Beta estrogen receptors

In general, there are more alpha receptors in regions involved in reproductive and sexual behaviors, such as:

• Hypothalamus
• Preoptic area
• Amygdala

These areas help regulate the release of hormones and control sexual behavior and reproductive function. 

Beta receptors are found in various brain regions, including:

• Hippocampus
• Cerebral cortex
• Cerebellum

The hippocampus is associated with learning and memory processes, while the cerebral cortex is involved in higher cognitive functions.

In your brain, estrogen:

• Promotes neurotrophin synthesis. Neurotrophins are proteins that act like fertilizers for your brain. They improve neuronal survival, growth, and functions.
• Modulates cholinergic and dopaminergic neurotransmitter systems
• Protects the brain from stress and inflammation. 
• Helps increase serotonin activity by increasing the number of serotonin receptors and enhancing the transport and uptake of serotonin. Serotonin plays a critical role in mood regulation.

Because estrogen is so important for brain functions, women in particular struggle with cognitive decline during menopause. Many menopausal symptoms (such as hot flashes) occur through the brain.

In many cases, hormone replacement can help restore verbal working memory and attention. 

It is important to note that hormone replacement therapy also comes with risks that should be weighed with your healthcare provider based on your individual health circumstances.

Men have estrogen receptors in their hippocampus, prefrontal cortex, and amygdala. These areas are important for memory, executive function, and emotional regulation. Estrogen promotes neural growth and synaptic plasticity. 

Men with higher levels of estradiol (a form of estrogen) have better verbal memory and executive function than men with lower levels.  As men age, the levels of estrogen fall, affecting cognitive abilities. 

Testosterone

Testosterone is the primary sex hormone responsible for developing and maintaining male physical and reproductive characteristics. Testosterone also plays many important roles in brain function. 

With age, testosterone levels in males decline. Men with higher levels of testosterone perform better on tests of spatial ability than men with lower levels. Supplementation may help improve cognitive function.

Testosterone is associated with improved spatial abilities. Testosterone and its metabolites exert a neuroprotective effect and prevent dendritic atrophy after the induced death of surrounding neurons. Testosterone depletion increases susceptibility to oxidative damage in the brain. 

A meta-analysis of 14 clinical trials explored the effects of testosterone supplementation on cognition in aging men. Researchers determined that, compared to a placebo group, testosterone supplementation:

• Improved executive functions like planning and problem-solving
• Increased cognitive performance and psychomotor speed

Although low testosterone levels are associated with cognitive decline, excessive levels are associated with increased aggression and impulsive behavior. So, it’s important to maintain optimal testosterone levels to ensure cognitive functions remain intact. 

Declining testosterone levels in women may lead to increased feelings of anxiety and unhappiness. In terms of cognitive function, testosterone seems to play a major role for women for:

• Spatial navigation
• Mental rotation – the ability to play with objects in your mind and see it from different angles

Testosterone therapy, however, does not seem as beneficial for the brains of aging women. A placebo-controlled study of 71 women post-hysterectomy explored the effects of testosterone supplementation on cognitive function. After 24 weeks of receiving testosterone injections, there were no differences in cognitive function between those who did and did not receive testosterone.

Progesterone

Progesterone receptors are found in key areas of the brain, including the hippocampus, amygdala, cerebellum, frontal cortex, hypothalamus, and thalamus. 

• Controls brain function and maintenance and has a neuroprotective effect on the brain.
• Enhance neuronal function by enhancing synaptic transmission and by forming and reducing synapses. 

Progesterone also acts on GABA (gamma amino butyric acid) receptors throughout the brain to produce a calming effect. GABA is the primary inhibitory transmitter in the brain and is responsible for reducing neuronal excitability throughout the nervous system. Increased progesterone levels increase GABA function and, therefore, more calming feelings.

Progesterone also promotes sleep by stimulating your brain to produce GABA. This helps calm and ease you into a state of relaxation. Many menopausal women have found that their sleep quality improves once they take progesterone.

Progesterone is a hormone primarily associated with the reproductive function in women, but it is also present in men, albeit in smaller quantities. It is involved in enhancing cognitive function. 

Progesterone has a neuroprotective effect on the brain: it protects neurons by acting as a free-radical scavenger, thereby decreasing the harm caused by free radicals.

Furthermore, Progesterone also modulates mood and behavior. 

Low progesterone levels in men may be associated with an increased risk of mood issues. In addition, progesterone has anti-anxiety and sedative effects due to its relationship with GABA, which may help to promote relaxation and sleep.

DHEA

Dehydroepiandrosterone (DHEA) is a hormone from the adrenal glands that can get converted into androgens and estrogens. DHEA levels decline with age.

One of the most important effects of DHEA on the brain is its potential neuroprotective properties. It protects against oxidative stress, which can cause damage to cells and tissues, including in the brain. DHEA treatment improves cognitive function and increases gray matter volume in the brains of older adults. 

DHEA has a strong influence on mood and stress management. Older adults who were given DHEA supplements experienced mood enhancement. 

DHEA has many potential benefits for the aging male brain, including neuroprotective effects, mood regulation, and stress reduction.

Pregnenolone

Pregnenolone is one of the most abundant neurosteroids in the body. It is produced naturally in the body, primarily in the adrenal gland and the gonads. It is a precursor to many other hormones, including testosterone, estrogen, and cortisol. Pregnenolone levels decline with age.

Pregnenolone exerts neuroprotective effects by protecting the brain against damage caused by stress and inflammation. Pregnenolone and its metabolites work on the amygdala and enhance neurocircuits related to mood and emotions. Furthermore, animal studies show that pregnenolone improves cognition by enhancing memory and learning.

Conclusion

These understandings of how closely hormones influence brain health, cognition, and nootropic responses led Mr. Noots to formulate DHeA/DHsheA. They are not just DHEA/pregnenolone supplements, but they’re also supercharged brain, hormone, and nutrition support for aging brains. If you suspect age-related hormonal declines could be keeping you from your full potential, definitely try these blends.

References:

1. Marrocco J, McEwen BS. Sex in the brain: hormones and sex differences. Dialogues Clin Neurosci. 2016;18(4):373-383. doi:10.31887/dcns.2016.18.4/jmarrocco
2. Gurvich C, Hoy K, Thomas N, Kulkarni J. Sex differences and the influence of sex hormones on cognition through adulthood and the aging process. Brain Sci. 2018;8(9):163. doi:10.3390/brainsci8090163
3. Zárate S, Stevnsner T, Gredilla R. Role of estrogen and other sex hormones in brain aging. Neuroprotection and DNA repair. Front Aging Neurosci. 2017;9:430. doi:10.3389/fnagi.2017.00430
4. Greendale GA, Wight RG, Huang MH, et al. Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. Am J Epidemiol. 2010;171(11):1214-1224. doi:10.1093/aje/kwq067
5. Weber MT, Maki PM, McDermott MP. Cognition and mood in perimenopause: a systematic review and meta-analysis. J Steroid Biochem Mol Biol. 2014;142:90-98. doi:10.1016/j.jsbmb.2013.06.001
6. Klosinski LP, Yao J, Yin F, et al. White matter lipids as a ketogenic fuel supply in aging female brain: Implications for Alzheimer’s disease. EBioMedicine. 2015;2(12):1888-1904. doi:10.1016/j.ebiom.2015.11.002
7. Goyal MS, Blazey TM, Su Y, et al. Persistent metabolic youth in the aging female brain. Proc Natl Acad Sci U S A. 2019;116(8):3251-3255. doi:10.1073/pnas.1815917116
8. Király A, Szabó N, Tóth E, et al. Male brain ages faster: the age and gender dependence of subcortical volumes. Brain Imaging Behav. 2016;10(3):901-910. doi:10.1007/s11682-015-9468-3
9. Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015;74:125-138. doi:10.1016/j.yhbeh.2015.06.010
10. Wharton W, Gleason CE, Olson SRMS, Carlsson CM, Asthana S. Neurobiological underpinnings of the estrogen – mood relationship. Curr Psychiatry Rev. 2012;8(3):247-256. doi:10.2174/157340012800792957
11. Maki PM, Thurston RC. Menopause and brain health: Hormonal changes are only part of the story. Front Neurol. 2020;11:562275. doi:10.3389/fneur.2020.562275
12. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002;87(11):5001-5007. doi:10.1210/jc.2002-020419
13. Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005;81(1):313S-316S. doi:10.1093/ajcn/81.1.313s
14. Celec P, Ostatníková D, Hodosy J. On the effects of testosterone on brain behavioral functions. Front Neurosci. 2015;9:12. doi:10.3389/fnins.2015.00012
15. Huang G, Wharton W, Travison TG, et al. Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial. J Endocrinol Invest. 2015;38(4):455-461. doi:10.1007/s40618-014-0213-3
16. Kapur J, Joshi S. Progesterone modulates neuronal excitability bidirectionally. Neurosci Lett. 2021;744(135619):135619. doi:10.1016/j.neulet.2020.135619
17. Nolan BJ, Liang B, Cheung AS. Efficacy of micronized progesterone for sleep: A systematic review and meta-analysis of randomized controlled trial data. J Clin Endocrinol Metab. 2021;106(4):942-951. doi:10.1210/clinem/dgaa873
18. Stein DG. Progesterone exerts neuroprotective effects after brain injury. Brain Res Rev. 2008;57(2):386-397. doi:10.1016/j.brainresrev.2007.06.012
19. Auger CJ, Forbes-Lorman RM. Progestin receptor-mediated reduction of anxiety-like behavior in male rats. PLoS One. 2008;3(11):e3606. doi:10.1371/journal.pone.0003606
20. Peltier MR, Sofuoglu M. Role of exogenous progesterone in the treatment of men and women with substance use disorders: A narrative review. CNS Drugs. 2018;32(5):421-435. doi:10.1007/s40263-018-0525-5
21. Wolkowitz OM, Reus VI, Roberts E, et al. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry. 1997;41(3):311-318. doi:10.1016/s0006-3223(96)00043-1
22. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry. 1999;156(4):646-649. doi:10.1176/ajp.156.4.646
23. Fisher A, Morley JE. Antiaging medicine: the good, the bad, and the ugly. J Gerontol A Biol Sci Med Sci. 2002;57(10):M636-9. doi:10.1093/gerona/57.10.m636
24. Murugan S, Jakka P, Namani S, Mujumdar V, Radhakrishnan G. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation. J Biol Chem. 2019;294(12):4596-4607. doi:10.1074/jbc.RA118.005543
25. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014;39(12):2867-2873. doi:10.1038/npp.2014.138
26. Vallée M, Mayo W, Le Moal M. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Rev. 2001;37(1-3):301-312. doi:10.1016/s0165-0173(01)00135-7

In Part 1, we explained the different cognitive functions and what neurotransmitters are essential to make them happen. Now, let’s talk about some strategies to help keep your cognitive functions in tip-top shape

Get Enough Shut Eye

Getting enough high-quality sleep is critical to support optimal cognitive functioning, and it can even enhance your performance beyond normal conditions. 

Sleep is critical to:

• Consolidate your memories – also leading to better learning and decision-making 
• Maintain focus and attention
• Facilitate language processing

In a literature review exploring the link between sleep and cognitive function, researchers highlighted that sleep not only strengthens our memories but also helps us to gain insights and make connections in large amounts of information.

Sleep also helps protect your brain. Think of sleep as the housekeeper of your brain. While you sleep, your brain resets inflammation and neurotransmitter receptors, allowing them to rest and regain sensitivity for during the day.

In Part 1, we talked about neuroplasticity and all of the new synaptic connections that can be made throughout the day. Sleep helps refine these synapses by eliminating excess ones to make them more efficient.

How much sleep is enough to preserve your cognitive functions? A study of 4,417 adults studied the effects of sleep on cognitive function. Those participants who slept less than six hours per night or more than nine hours per night had worse cognitive function than those who slept between seven and eight hours per night.

Ideally, you should aim for seven to eight hours per night. Check out this article to learn all about The Stages of Sleep and Why You Need All of Them for Health and Cognitive Function.

Stay Curious and Exercise Your Brain

Curiosity is the basis of our cognitive function. It’s what drives motivation and pushes us to learn more about the world around us. You learn better when you are curious about something. Your hippocampus becomes active when you are curious in anticipation of learning and helps strengthen your memory. 

Curiosity drives you to learn more and learn things more thoroughly. While researchers are just beginning to explore how curiosity boosts cognitive function, they believe it’s highly promising.

Some strategies to stay curious include:

1. Ask questions, constantly
2. When you are curious about something, go down that rabbit hole
3. Listen actively to the people around you
4. Looks at the things around you rather than your phone
5. Memorize facts and information
6. Rather than focusing on being right in a conversation, focus on understanding.

Exercise

Staying active and engaging in physical exercise promotes healthy cognitive function and well-being. It also improves your neuroplasticity which increases your ability to make new connections.

Critical to brain health are neurotrophins, which help your neurons survive and grow and are critical for the proper development of your nervous system.  Some of the most important ones are:

• Nerve growth factor (NGF): essential for the development and maintenance of sympathetic and sensory neurons
• Brain-derived neurotrophic factor (BDNF): initiates neuron growth and is essential for learning and memory
• Neurotrophin-3: promotes the differentiation of neurons into various types of neurons
• Neurotrophin-4: augments the serotonin, dopamine, and GABA systems

The release of BDNF, in particular, increases with exercise. This means that when you get active, you are boosting your cognitive functions.

A study of 128,925 individuals explored the connection between physical activity and cognitive decline. Subjects who were less active experienced a more significant reduction in cognitive health. In fact, cognitive decline was twice as common in those who were inactive compared to those who stayed physically active.

Getting at least 150 minutes of moderate-intensity physical activity per week can help boost your cognitive function.

Supplements

Beyond lifestyle changes, adding brain-boosting supplements to your daily routine will help keep your brain sharp. 

CollaGenius

CollaGenius is an exciting blend of five superfoods, including four types of mushrooms and collagen. 

Collagen helps improve brain structure and cognitive language function. In a study of 30 healthy adults, participants took five grams of collagen daily for four weeks. Participants experienced improved brain structure and cognitive function.

Scientists recognize many mushrooms for their medicinal properties and many have been in use for thousands of years. As you age, you naturally experience neuron death and, with that, a loss in cognitive function. Medicinal mushrooms can support neuron growth and survival as well as neuroplasticity.

Lion’s mane is the star of the show in this mushroom blend. A literature review exploring the benefits of mushrooms on cognitive function highlights the effects of this mushroom. Researchers determined that lion’s mane may:

• Reduce cell death
• Act as a neuroprotector
• Improve cognitive impairment
• Promote nerve growth

You can get all these health benefits and much more by taking CollaGenius daily. 

Magnesium

Magnesium plays a critical role in your central nervous system by regulating NMDA (N-methyl-D-aspartate) receptors in your brain. The health of these receptors is vital for fast neuron firing, neuroplasticity, and preventing neurodegeneration.

Magnesium may also support oxidative stress and neuroinflammation balances, which can affect your cognitive function.

A study of 2,508 individuals explored the connection between magnesium intake and cognition. The more magnesium individuals took, the higher their cognitive score. The highest cognitive scores were those who took over 400 mg of magnesium daily.

You can get an excellent source of magnesium with Magnesium Breakthrough. It contains all seven forms of magnesium to ensure you’ve got your bases covered and can optimally support your cognitive function. 

Probiotics

Probiotics aren’t just for gut health. They can be excellent cognitive support as well! Your gut has a direct connection to your brain and vice versa, called the gut-brain-microbiota axis. Your gut can produce neurotransmitters that affect your cognitive function.

A literature review of 30 studies set out to explore the effects of probiotics on cognitive function. The majority of studies demonstrated an improvement in at least one cognitive function. Probiotics may protect against stress-induced cognitive decline and enhance cognitive functioning.

Some probiotic strains highlighted by the study include:

• Lactobacillus 
• Bifidobacterium
• Lactiplantibacillus plantarum (L. plantarum) – This strain was particularly highlighted for restoring cognitive function in impaired patients. It also survives well and colonizes the digestive tract more easily than other probiotics.

CogniBiotics contains not only the probiotics mentioned above but also a powerful blend of 17 herbs known to support your mood and enhance cognitive function. CogniBiotics is the only probiotic-nootropic blend on the market that improves the entire gut-brain-microbiota axis.

The Chinese herbs included in this blend, like Polygonum multiflorum, Salvia miltiorrhiza, and Rehmannia glutinosa, can help increase neurotransmitter acetylcholine levels while also protecting your neurons against oxidative stress and improve neurotransmitter balance. 

Digestive Support

We already mentioned the importance of the gut-brain-microbiota axis. When you experience gut dysbiosis, an imbalance in your gut microbiome, you are more likely to struggle with learning and long-term memory. Taking digestive enzymes can help balance your gut microbiome and energy metabolism, improving your brain health.

When you take digestive enzymes, they break down your food to prevent partially digested foods from crossing the lining of your intestines. Many healthy people get some minor inflammation from foods, which can interfere with optimal cognitive functions. 

An excellent source of brain-boosting enzymes is kApex. It contains a blend of digestive enzymes designed to break down fats and proteins while improving your energy and cognitive function. 

Nootropics

A literature review exploring nootropics as cognitive enhancers determined they can successfully improve cognitive function, especially when there is a deficiency present. The positive effects of nootropics build over time, and with rare side effects, they are a great tool to turn to.

You can find the perfect nootropic formula or stack personalized to boost your brain power with Nootopia. Taking just a five-minute quiz can help determine what neurotransmitter support you need most. Expertly designed formulas focus on what you want to improve, like:

• NectarX: designed to stimulate brain cells and support healthy functions of serotonin, dopamine, and acetylcholine
• Ultimate Focus: works to optimize your dopamine levels to keep you motivated and focused
• GABAlicious: supports healthy GABA levels and increases your verbal fluency while simultaneously calming you down
• Zamner Juice: expands your mind to see new possibilities by supporting healthy dopamine, serotonin, and GABA functions
• Brain Flow: optimizes your serotonin, dopamine, and GABA production to boost your mental endurance and enhance your memory while keeping you focused

Stress Management and Support

Your cognitive functions can decrease when you’re stressed. A study of over 24,000 individuals explored the effects of stress on cognitive functions. When subjects experienced stress, their risk of cognitive decline increased, including their memory and attention

As part of your stress response, your body releases cortisol. A literature review examining the effects of cortisol on cognitive functions determined that higher cortisol levels lead to poor overall cognitive functioning and can cause faster age-related cognitive decline.

While you can’t completely eliminate stress from your life, you can take steps to manage your stress in healthy ways. Here are some research-backed strategies for stress reduction:

• Mindfulness
• Yoga
• Meditation
• Listening to music
• Spending time in nature

Adaptogen supplements such as Cognibiotics can also support a balanced stress response and may mitigate some negative health effects of stress.

Takeaway

Maintaining optimal cognitive functions is essential for you to carry out daily tasks effectively and be a superstar professionally. When you aren’t at your best, it affects your learning, memory, and ability to make good decisions and communicate effectively.  To maintain or increase cognitive function, it’s essential to:

• Get high-quality sleep every night.
• Exercise regularly.
• Stay curious.
• Take brain-boosting supplements to keep you at your very best.
• Manage your stress with practices like mindfulness or yoga.
• Take this five-minute quiz to help determine what neurotransmitter support you need most.

References:

1. Diekelmann S. Sleep for cognitive enhancement. Front Syst Neurosci. 2014;8:46. doi:10.3389/fnsys.2014.00046
2. Deak MC, Stickgold R. Sleep and cognition: Sleep and cognition. Wiley Interdiscip Rev Cogn Sci. 2010;1(4):491-500. doi:10.1002/wcs.52
3. Eugene, A. R., & Masiak, J. The Neuroprotective Aspects of Sleep. MEDtube science. 2015;3(1):35-40.
4. Weiss JT, Donlea JM. Roles for sleep in neural and behavioral plasticity: Reviewing variation in the consequences of sleep loss. Front Behav Neurosci. 2021;15:777799. doi:10.3389/fnbeh.2021.777799
5. Slomski A. Sleep duration tied to adverse outcomes for older adults. JAMA. 2021;326(17):1666. doi:10.1001/jama.2021.19071
6. Gruber MJ, Gelman BD, Ranganath C. States of curiosity modulate hippocampus-dependent learning via the dopaminergic circuit. Neuron. 2014;84(2):486-496. doi:10.1016/j.neuron.2014.08.060
7. Kidd C, Hayden BY. The psychology and neuroscience of curiosity. Neuron. 2015;88(3):449-460. doi:10.1016/j.neuron.2015.09.010
8. Mandolesi L, Polverino A, Montuori S, et al. Effects of physical exercise on cognitive functioning and wellbeing: Biological and psychological benefits. Front Psychol. 2018;9. doi:10.3389/fpsyg.2018.00509
9. Bazan JF, Wiesmann C. The mechanism of NGF signaling suggested by the p75 and TrkA receptor complexes. In: Handbook of Cell Signaling. Elsevier; 2010:277-285.
10. Brigadski T, Leßmann V. BDNF: a regulator of learning and memory processes with clinical potential. eNeuroforum. 2014;5(1):1-11. doi:10.1007/s13295-014-0053-9
11. Hata T, AboEllail MA. Antenatal fetal neurodevelopment test. In: Diagnosis, Management and Modeling of Neurodevelopmental Disorders. Elsevier; 2021:367-375.
12. Altar CA, Boylan CB, Fritsche M, Jackson C, Hyman C, Lindsay RM. The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic systems during behaviorally effective infusions to the substantia nigra. Exp Neurol. 1994;130(1):31-40. doi:10.1006/exnr.1994.1182
13. Lippi G, Mattiuzzi C, Sanchis-Gomar F. Updated overview on interplay between physical exercise, neurotrophins, and cognitive function in humans. J Sport Health Sci. 2020;9(1):74-81. doi:10.1016/j.jshs.2019.07.012
14. Omura JD, Brown DR, McGuire LC, Taylor CA, Fulton JE, Carlson SA. Cross-sectional association between physical activity level and subjective cognitive decline among US adults aged ≥45 years, 2015. Prev Med. 2020;141(106279):106279. doi:10.1016/j.ypmed.2020.106279
15. Current guidelines. Health.gov. Accessed May 17, 2023. https://health.gov/our-work/nutrition-physical-activity/physical-activity-guidelines/current-guidelines
16. Koizumi S, Inoue N, Sugihara F, Igase M. Effects of collagen hydrolysates on human brain structure and cognitive function: A pilot clinical study. Nutrients. 2019;12(1):50. doi:10.3390/nu12010050
17. Sabaratnam V, Kah-Hui W, Naidu M, Rosie David P. Neuronal health – can culinary and medicinal mushrooms help? J Tradit Complement Med. 2013;3(1):62-68. doi:10.4103/2225-4110.106549
18. Li IC, Lee LY, Tzeng TT, et al. Neurohealth properties ofHericium erinaceusMycelia enriched with erinacines. Behav Neurol. 2018;2018:1-10. doi:10.1155/2018/5802634
19. Tao MH, Liu J, Cervantes D. Association between magnesium intake and cognition in US older adults: National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. Alzheimers Dement (N Y). 2022;8(1):e12250. doi:10.1002/trc2.12250
20. Eastwood J, Walton G, Van Hemert S, Williams C, Lamport D. The effect of probiotics on cognitive function across the human lifespan: A systematic review. Neurosci Biobehav Rev. 2021;128:311-327. doi:10.1016/j.neubiorev.2021.06.032
21. Menden A, Hall D, Hahn-Townsend C, et al. Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer’s disease-like pathology in APP/PS1 mice. Sci Rep. 2022;12(1):4797. doi:10.1038/s41598-022-08840-7
22. Malík M, Tlustoš P. Nootropics as cognitive enhancers: Types, dosage and side effects of smart drugs. Nutrients. 2022;14(16):3367. doi:10.3390/nu14163367
23. Kulshreshtha A, Alonso A, McClure LA, Hajjar I, Manly JJ, Judd S. Association of stress with cognitive function among older Black and White US adults. JAMA Netw Open. 2023;6(3):e231860. doi:10.1001/jamanetworkopen.2023.1860
24. Ouanes S, Popp J. High cortisol and the risk of dementia and Alzheimer’s disease: A review of the literature. Front Aging Neurosci. 2019;11:43. doi:10.3389/fnagi.2019.00043
25. Sharma M, Rush SE. Mindfulness-based stress reduction as a stress management intervention for healthy individuals: a systematic review: A systematic review. J Evid Based Complementary Altern Med. 2014;19(4):271-286. doi:10.1177/2156587214543143
26. Woodyard C. Exploring the therapeutic effects of yoga and its ability to increase quality of life. Int J Yoga. 2011;4(2):49-54. doi:10.4103/0973-6131.85485
27. Goyal M, Singh S, Sibinga EMS, et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis: A systematic review and meta-analysis. JAMA Intern Med. 2014;174(3):357-368. doi:10.1001/jamainternmed.2013.13018
28. de Witte M, Spruit A, van Hooren S, Moonen X, Stams GJ. Effects of music interventions on stress-related outcomes: a systematic review and two meta-analyses. Health Psychol Rev. 2020;14(2):294-324. doi:10.1080/17437199.2019.1627897

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