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The Glymphatic System: How to Detox Your Brain & Reverse the Root Cause of Cognitive Impairment

The Glymphatic System: How to Detox Your Brain & Reverse the Root Cause of Cognitive Impairment

Your brain is a complex organ that performs many functions essential to your everyday life. Among its many responsibilities, the brain must manage cognitive processes such as learning and memory, regulate emotions, and coordinate movement.

As you age, it’s not uncommon for some of these functions to decline. One of the root causes of cognitive impairment is a build-up of toxins in the brain. Enter your glymphatic system, a waste elimination pathway responsible for taking out the metabolic trash in your brain.

With a bit of biohacking, optimizing this clean-up process may help prevent or even reverse cognitive impairment. In this blog post, we will discuss what the glymphatic system is, how it works, and some key steps you can take to help reverse the root cause of cognitive decline.

What Is the Glymphatic System?

The glymphatic system is a waste management pathway in the brain that is responsible for clearing out toxins while also delivering growth factors, glucose, lipids, neuromodulators, amino acids, and other compounds1. What makes the glymphatic system unique is that it uses a network of tunnels created by astroglial cells (brain cells responsible for support and protection of neurons) as a transport medium to remove toxins.

You may be familiar with the lymphatic system, which removes metabolic waste from the interstitial space (gaps between cells) throughout your body. Until recently, it was widely believed the lymphatic system was absent from the central nervous system.

So, in 2012, when researchers discovered a similar system within glial cells in the brain and spinal cord, they concluded it performed the same cleansing function as the lymphatic system does for the rest of the body. And they called it the glymphatic system. Then in 2015, through new methods, researchers were able to prove there were, in fact, unique lymphatic vessels in the CNS2,3.

Now the interaction between the glymphatic system and the meningeal lymphatic system is a promising area of research, especially as it relates to cognitive impairment.

How Does the Glymphatic System Work?

The glymphatic system works by circulating cerebrospinal fluid (CSF) through the brain. CSF is a clear, colorless liquid that bathes and protects the brain and spinal cord. It contains various proteins, nutrients, minerals, and antibodies that help support nerve function and protect against infection.

As CSF is flushed through the brain, it collects toxins and other waste products from interstitial fluid4. The glymphatic system connects to the meningeal lymphatic system to transport the CSF to cervical lymph nodes where the waste is then removed from the body via the circulatory system.

While there are other outflow mechanisms the CSF uses to reach the blood, such as arachnoid granulations, the lymphatic pathways are the primary route5,6. However, aging reduces the effectiveness of this process, and impaired outflow is being investigated as a contributing factor in cognitive impairment.

While a number of important questions remain unanswered regarding CSF production, circulation, and absorption via the glymphatic and meningeal lymphatic systems, what is important to note is that when the glymphatic system is not working properly, toxic proteins, such as amyloid plaques and neurofibrillary tangles are not removed from the brain.

The build-up of these toxic proteins is the leading indicator of cognitive impairment and conditions such as Alzheimer’s disease (AD)8. Therefore, optimizing the glymphatic system’s clean-up process with new and traditional detoxification therapies and biohacking methods could help prevent and/or reverse degeneration of brain function, leading to better cognitive health throughout the entire lifespan, which continues to increase with each generation.  

What Is Biohacking the Brain?

Biohacking is a term used to describe the process of using science and technology as a means to improve biological performance9. Over time, biohacking has evolved into a broader health-related discipline with individuals taking on their own personal experiments and implementing interventions like diet and exercise changes to achieve optimal cognitive function, longevity, and greater human potential.

While biohacking is not new, what makes modern biohacking so interesting is its ability to bring a mixture of ancient wisdom and cutting-edge technology together in one space. While new biohacks like the ketogenic diet, wearable technology, and brain stimulation continue to emerge, there are some that date back thousands of years, such as fasting.

What this means for cognitive health is that we have the freedom to look at interventions for cognitive impairment and enhancement from all angles (traditional western medicine vs. eastern medicine, for example) and find the best possible solutions for each individual based on their genetic profile.

What Is Epigenetics and What Does It Have to Do with Biohacking the Brain?

Since 1942, the field of epigenetics has explored the interaction of genes with their environment10. Epigenetics shows that you can change the expression of your genes by changing your internal and external environments11.

With epigenetics, you have the ability to take biohacking a step further by intentionally altering your environment in order to turn specific genes on or off. In essence, by biohacking with epigenetics, you can take control of the biochemical factors that influence cognitive health, including the glymphatic system’s detoxification process.

A key epigenetic factor known to play a role in cognitive health is DNA methylation. Methylation is the process of adding a methyl group to a DNA base. It’s involved in many critical processes including DNA repair, gene expression, and controlling inflammation. Other epigenetic factors that play a role in cognitive health include histone acetylation, long noncoding RNAs, and noncoding microRNAs (miRNAs) expression.

When these factors are impaired, it can lead to problems like cognitive decline and Alzheimer’s disease13. For example, reduced methylation of apolipoprotein E (APOE), a gene that plays a pivotal role in the glymphatic system’s removal of β-amyloid plaque from the brain14,15,16, is linked to AD and Lewy body dementia due to the way it affects lipid metabolism in the brain .

While further investigation is needed to understand how APOE4, the glymphatic, and meningeal lymphatic systems are interconnected, biohacking with epigenetics to suppress the expression of APOE4 may lead to proper uptake and clearance of harmful Aβ plaques17.

Another important gene in glymphatic function is AQP4. It controls aquaporin 4 water channels, which is where CSF and the toxic interstitial fluid are exchanged on the end feet of astrocytes that wrap around meningeal lymphatic vessels18.

In the latter stages of AD, for example, the loss of polarity of AQP4 reduces glymphatic function. Researchers are also observing how people with AQP4 genetic variations have poor sleep patterns and higher levels of Aβ plaque accumulation as a result of dysfunctional glymphatic systems19.

While these are just two of several genes that researchers are studying as it relates to the clearance of neurotoxic proteins from the brain, they just may hold the key to biohacking the glymphatic system and reversing the root cause of cognitive impairment.

Practical Biohacks for the Glymphatic System

Now that we’ve covered the basics of the glymphatic system and epigenetics, let’s take a look at three practical biohacking approaches you can use to enhance glymphatic function. These are some of the most popular methods being explored by DIY biologists (biohackers) and researchers today:

  1. Biohack Your Sleep: Sounds too simple, right? But, the glymphatic system is only fully active during sleep. In fact, imaging has shown glymphatic clearance slows as much as 90% during waking hours20. During sleep, the interstitial space in your brain increases up to 60% due largely to the decline of norepinephrine21. This allows for a greater flow of cerebrospinal fluid and, in turn, increased Aβ plaque clearance accompanied by fresh, new CSF with all the beneficial compounds flowing into your brain22.

    So, sleep quality and quantity matter, with quiescent or non-rapid eye movement sleep being the goal. If you suffer from insomnia or other sleep disturbances, you may want to consider a wearable device such as a FitBit or Oura Ring. These biohacking technologies allow you to track your sleep patterns so you can assess where you can make changes to your bedroom environment, your sleep position, what you eat before your head hits the pillow, or at what point in your day you exercise to get your best sleep and optimize glymphatic detoxification.

    Completely blacking out all natural and artificial light from your bedroom, using a white noise machine, ending screen time at least 90 minutes before bed, reducing EMF in your bedroom by turning off all wifi routers in your home, as well as your cellular devices all the way off (not just to airplane mode) are simple hacks to turn into daily habits that will help you get deeper sleep without having to make a big investment or make drastic changes to your lifestyle.
  1. Biohack Your Stress Response: Stress is a hindrance to developing and maintaining healthy sleep patterns, which already negatively impacts glymphatic detoxification. But beyond that, other stress-related changes to glial cells may contribute to toxic accumulation of metabolic waste. How stress impacts these processes is not fully understood.

But the finding that adult emotional depression is linked to childhood stressors suggests stress causes epigenetic or neural changes23.  We do know stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which releases glucocorticoids.

And a dysfunctional HPA axis, as indicated by elevated blood cortisol levels, is indicative of AD24. Chronic stress was shown to reduce polarization and expression of AQP4 as well as AQP4 transcription, which, as mentioned, is associated with glymphatic dysfunction25.

Add to that the fact that severe life stress leads to another kind of stress in the brain, namely oxidative stress. When the generation of oxidants and the response of antioxidants becomes imbalanced in the CNS, systemic oxidative stress occurs. 26

And this reduces the efficacy of glymphatic detoxification.27 So, biohacking your stress response is a worthy approach to glymphatic system health.  Here are a few DIY hacks to shape your biological response to stress:

  • Exercise Outdoors: While exercise could be classified as its own glymphatic system biohack, pairing it with time outside takes it up an epigenetic notch. Researchers are studying the importance of certain types of exercise and how they  lead to epigenetic changes in DNA methylation and the expression of specific miRNAs, which produce beneficial metabolic alterations that improve cognitive function28,29.  Add biohacking methods like frequent fresh air immersion, earthing, and forest bathing, which are proven to lower cortisol levels, by exercising outside, and you can intentionally take your stress levels down a notch30.
  • Practice Gratitude: I talk about several ways to practice gratitude in this article. In short, research shows that being thankful can enhance your health, improve your physical well-being, and even prevent chronic illness.31
  • Meditation: Mind-body medicine practices such as meditation and chanting are ancient biohacks that are now being augmented by computer software. You can download meditation apps on your phone to optimize your minutes in meditation. But how does this impact glymphatic detoxification? The answer, in part, is by reducing stress. But it is interesting to note that the NIH is offering funding to researchers for the study of how complementary and integrative medicine approaches such as mediation affect glymphatic and meningeal lymphatic mechanisms, including toxic material clearance in neurodegenerative diseases and the aging brain32.
  1. Biohack Your Diet Supplementation: Ever heard of nootropics? These are compounds that enhance cognitive function. From the everyday like caffeine to the exotic, such as lion’s mane mushroom, nootropics have been used for centuries by indigenous cultures around the world to promote mental clarity and improve memory. Now biohackers are using nootropics for their cognitive health and enhancement properties.

A growing body of research is demonstrating how certain supplements can support glymphatic clearance, especially in people with reduced function due to sleep disturbances or genetic variations that inhibit its optimum potential. For example:

  • Acetyl-L-Carnitine: Lowers oxidative stress and prevents subsequent apoptosis (cell death)33
  • Bacopa: Traditionally used in Ayurvedic medicine to treat neurological defects, may reduce oxidative stress and mitochondrial dysfunction34
  • Gingko: Improves mitochondrial function and the apoptotic pathway35
  • L-Theanine: An amino acid that promotes calmness, relaxation, and a feeling of well-being
  • Melatonin:  Reverses low-level inflammation linked to age-related neurodegenerative disorders36
  • Omega-3: Modulates inflammation and glymphatic activity37
  • Phosphatidylserine: A phospholipid that when paired with Omega-3 can reduce cortisol, regulate sleep quality, and preserve or enhance brain function38
  • Pyrroloquinoline quinone (PQQ): Improves concentration, focus, and longevity
  • Rhodiola: Decreases the effects of stress and has anti-inflammatory, anti-aging, and immunostimulatory properties39
  • Rosemary: Yes, this common herb can protect neurons from inflammation and Aβ plaque formation as well as inhibit neuronal apoptosis40
  • Vitamin D: Neuroprotective, anti-inflammatory, and antioxidant properties, including inhibition of amyloid formation and enhancement of amyloid clearance41

Supplementing with these nootropics and eating a diet rich in DHA and EPA omega-fatty acids as well as low in saturated fats can make a significant impact on the function of your glymphatic-meningeal lymphatic system.

Conclusion

So there you have it…a few practical biohacks you can do to support your glymphatic system and help prevent and/or reverse the root cause of cognitive decline. But this is just the tip of the iceberg. What we know about the glymphatic system is constantly evolving.  Keep your eyes open for future Silver Tree Wellness Center blogs for the most up-to-date research, bringing science and spirit together to support natural healing.

And remember, if you are experiencing sleep disturbances, signs of aging, or cognitive decline, please consult with a trusted healthcare professional or call SilverTree today to make an appointment.

References

  1. https://pubmed.ncbi.nlm.nih.gov/25947369/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506234/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493418/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755861/
  5. https://www.nature.com/articles/s41598-018-25666-4
  6. https://www.nature.com/articles/s41467-017-01484-6
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891904/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694579/
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226663/
  10. https://pubmed.ncbi.nlm.nih.gov/22186258/
  11. https://www.ncbi.nlm.nih.gov/books/NBK532999/
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983821/
  13. https://www.frontiersin.org/articles/10.3389/fphar.2019.00665/full
  14. https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2018.02.005
  15. https://www.nature.com/articles/s41380-020-0731-7
  16. https://www.nih.gov/news-events/nih-research-matters/study-reveals-how-apoe4-gene-may-increase-risk-dement
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456907/  
  18. https://elifesciences.org/articles/40070
  19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865132/
  20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/
  21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/
  22. https://pubmed.ncbi.nlm.nih.gov/24136970/
  23. https://www.hindawi.com/journals/np/si/142309/
  24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/
  25. https://pubmed.ncbi.nlm.nih.gov/30607477/
  26. https://docs.google.com/document/d/1TEg2CQvTS-jylQLtnYJCIlAt9Q88e1mAbxgtBdFw9Pg/edit#
  27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904342/
  28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921698/
  29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705447/
  30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981243/
  31. https://www.tandfonline.com/doi/abs/10.1080/17439760.2017.1326520?journalCode=rpos20
  32. https://www.nccih.nih.gov/grants/concepts/consider/mechanisms-underlying-modulation-of-the-glymphatic-and-lymphatic-systems-by-complementary-and-integrative-health-approaches
  33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621476/
  34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564646/
  35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694352/    
  36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646522/
  37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/
  38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942871/
  39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208354/
  40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749867/
  41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210535/