How to optimise your brain's waste disposal system
New research suggests that body posture during sleep may affect the efficiency of the brain’s self-cleaning process
Cairo's zabaleen collect the city's waste on donkey carts.
Cairo’s zabaleen collect the city’s waste on donkey carts. Photograph: Dave Stamboulis/Alamy
Mo Costandi
@mocost
Saturday 22 August 2015 09.00 BST Last modified on Saturday 22 August 2015 19.42 BST
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The human brain can be compared to something like a big, bustling city. It has workers, the neurons and glial cells which co-operate with each other to process information; it has offices, the clusters of cells that work together to achieve specific tasks; it has highways, the fibre bundles that transfer information across long distances; and it has centralised hubs, the densely interconnected nodes that integrate information from its distributed networks.
Like any big city, the brain also produces large amounts of waste products, which have to be cleared away so that they do not clog up its delicate moving parts. Until very recently, though, we knew very little about how this happens. The brain’s waste disposal system has now been identified. We now know that it operates while we sleep at night, just like the waste collectors in most big cities, and the latest research suggests that certain sleeping positions might make it more efficient.
Newly discovered vessels beneath skull could link brain and immune system
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Waste from the rest of the body is cleared away by the lymphatic system, which makes and transports a fluid called lymph. The lymphatic system is an important component of the immune system. Lymph contains white blood cells that can kill microbes and mop up their remains and other cellular debris. It is carried in branching vessels to every organ and body part, and passes through them, via the spaces between their cells, picking up waste materials. It is then drained, filtered, and recirculated.
The brain was thought to lack lymphatic vessels altogether, and so its waste disposal system proved to be far more elusive. Several years ago, however, Maiken Nedergaard of the University of Rochester Medical Center and colleagues identified a system of hydraulic “pipes” running alongside blood vessels in the mouse brain. Using in vivo two-photon imaging to trace the movements of fluorescent markers, they showed that these vessels carry cerebrospinal fluid around the brain, and that the fluid enters inter-cellular spaces in the brain tissue, picking up waste on its way.
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Nedergaard and her colleagues also discovered that proper function of these vessels depends on movements of water around the brain, which are carried out by glial cells called astrocytes, and therefore named them the glymphatic system. They went on to show that inter-cellular spaces expand by up to 60% in the brains of naturally sleeping and anaesthetised mice, and that this expansion drives the clearance of waste from the brain by facilitating the movements of lymph and water.
Last month, researchers from the University of Virginia reported the identification of lymphatic vessels in the central nervous system. They demonstrated that the lymphatic system extends into the dura mater, the thickest and outer-most of the three meningeal membranes that envelope the brain and spinal cord. These vessels run parallel to the major veins and arteries, and split to send branches deep into the brain’s crevices. The researchers believe that they could be linked to the glymphatic system, and may be the second stage of the disposal mechanism, which would transport waste out of the brain and spinal cord altogether.
The latest study from Nedergaard’s group, published in the Journal of Neuroscience earlier this month, shows that body posture affects the efficiency of the glymphatic system’s waste clearance. Using fluorescence microscopy and radioactive tracing once again, they showed that drainage of the cerebrospinal fluid worked best in mice lying on their sides compared to those lying on their back or standing up.
The neuroprotective lifestyle
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The function of sleep was once deeply mysterious, but there’s plenty of evidence that it is critical for memory consolidation, and it would now seem to be required for the effective removal of waste from the brain, too. Although these studies were performed in mice, preliminary results suggest that lymphatic vessels are also present in the human brain and spinal cord, but further research will be needed to confirm that they actually constitute a working waste disposal system.
Eventually, the link to sleep could have important implications for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, all of which involve the build-up of misfolded proteins within and around nerve cells, because of a defective waste disposal system. Indeed, it is now seems clear that good sleep hygiene has a neuroprotective effect and, in line with this, other research shows that sleep disturbances predict the onset of neurodegeneration.
Sleeping on the side just happens to be the most popular sleeping posture for both mice and humans, and so this preference may have evolved to optimise the waste disposal system and thus ensure that the metropolis of the brain runs as effectively as possible.
References
Lee, H. et al. (2015). The Effect of Body Posture on Brain Glymphatic Transport. J. Neurosci, 35: 11034-44. DOI: 10.1523/JNEUROSCI.1625-15.2015.
Louveau, A., et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523: 337-41. DOI: 10.1038/nature14432.
Xu, L., et al. (2014). Sleep Drives Metabolite Clearance from the Adult Brain. Science, 342: 373-7. DOI: 10.1126/science.1241224. [Full text]
Iliff, J., et al. (2013). A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Sci. Trans. Med., 4: 147ra111. DOI: 10.1126/scitranslmed.3003748. [Full text]
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Neuroscience Health
Thursday, October 17, 2013
Brain may flush out toxins during sleep
NIH-funded study suggests sleep clears brain of damaging molecules associated with neurodegeneration.
Image of a mouse brain
Scientists watched dye flow through the brain of a sleeping mouse.Nedergaard Lab, University of Rochester Medical Center.
A good night’s rest may literally clear the mind. Using mice, researchers showed for the first time that the space between brain cells may increase during sleep, allowing the brain to flush out toxins that build up during waking hours. These results suggest a new role for sleep in health and disease. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH.
“Sleep changes the cellular structure of the brain. It appears to be a completely different state,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center in New York, and a leader of the study.
For centuries, scientists and philosophers have wondered why people sleep and how it affects the brain. Only recently have scientists shown that sleep is important for storing memories. In this study, Dr. Nedergaard and her colleagues unexpectedly found that sleep may be also be the period when the brain cleanses itself of toxic molecules.
Their results, published in Science, show that during sleep a plumbing system called the glymphatic system may open, letting fluid flow rapidly through the brain. Dr. Nedergaard’s lab recently discovered the glymphatic system helps control the flow of cerebrospinal fluid (CSF), a clear liquid surrounding the brain and spinal cord.
“It’s as if Dr. Nedergaard and her colleagues have uncovered a network of hidden caves and these exciting results highlight the potential importance of the network in normal brain function,” said Roderick Corriveau, Ph.D., a program director at NINDS.
Initially the researchers studied the system by injecting dye into the CSF of mice and watching it flow through their brains while simultaneously monitoring electrical brain activity. The dye flowed rapidly when the mice were unconscious, either asleep or anesthetized. In contrast, the dye barely flowed when the same mice were awake.
“We were surprised by how little flow there was into the brain when the mice were awake,” said Dr. Nedergaard. “It suggested that the space between brain cells changed greatly between conscious and unconscious states.”
To test this idea, the researchers inserted electrodes into the brain to directly measure the space between brain cells. They found that the space inside the brains increased by 60 percent when the mice were asleep or anesthetized.
“These are some dramatic changes in extracellular space,” said Charles Nicholson, Ph.D., a professor at New York University’s Langone Medical Center and an expert in measuring the dynamics of brain fluid flow and how it influences nerve cell communication.
Certain brain cells, called glia, control flow through the glymphatic system by shrinking or swelling. Noradrenaline is an arousing hormone that is also known to control cell volume. Similar to using anesthesia, treating awake mice with drugs that block noradrenaline induced unconsciousness and increased brain fluid flow and the space between cells, further supporting the link between the glymphatic system and consciousness.
Previous studies suggest that toxic molecules involved in neurodegenerative disorders accumulate in the space between brain cells. In this study, the researchers tested whether the glymphatic system controls this by injecting mice with labeled beta-amyloid, a protein associated with Alzheimer’s disease, and measuring how long it lasted in their brains when they were asleep or awake. Beta-amyloid disappeared faster in mice brains when the mice were asleep, suggesting sleep normally clears toxic molecules from the brain.
“These results may have broad implications for multiple neurological disorders,” said Jim Koenig, Ph.D., a program director at NINDS. “This means the cells regulating the glymphatic system may be new targets for treating a range of disorders.”
The results may also highlight the importance of sleep.
“We need sleep. It cleans up the brain,” said Dr. Nedergaard.
This work was supported by grants from the NINDS (NS078167, NS07830, NS028642).
For more information about neurological disorders and the latest neuroscience research: http://www.ninds.nih.gov
NINDS is the nation’s leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH…Turning Discovery Into Health®
Reference
Xie et al “Sleep initiated fluid flux drives metabolite clearance from the adult brain.” Science, October 18, 2013. DOI: 10.1126/science.1241224
How To Detox Your Brain By Hacking Your Glymphatic System1
glymphatic system
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Wonder why you’re always reading about how important sleep quality is – not just quantity? Well, modern science still doesn’t know all of the molecular mechanisms behind why we need sleep. As of last month, we now know more.
A study, published in Science in October 2013 and entitled “Sleep Drives Metabolite Clearance from the Adult Brain,” finds just that: we need to sleep specifically so that the brain can focus on cleaning itself out each night.
Lead study author Dr. Maiken Nedergaard summarizes in a statement: “the restorative nature of sleep appears to be the result of the active clearance of the by-products of neural activity that accumulate during wakefulness.”[i]
The study’s abstract states (bolding is mine):
We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of ?-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.[ii]
While you rest, your brain is busy sweeping the floor, washing the dishes, and taking out the trash to prepare itself for the next day.
Your Glymphatic System: The Good Kind of “Brain Drain”
You probably haven’t read much about the glymphatic system because it hasn’t hit the mainstream, but you will. I covered this system, and how to hack it with food, in The Bulletproof Diet book. (If you order it on Amazon now and send me the receipt before midnight on December 1st, you get a bunch of free stuff).
In 2012, researchers identified this new maintenance system called the glymphatic system, which uses the cells’ mitochondria to remove cellular waste from the brain.[iii][iv] It found that the clear cerebrospinal fluid (CSF) in the brain is what is responsible for draining toxins from the brain, much like how the lymph system in other organs is what removes waste from those cells to the kidney and liver. But the brain has no lymph – it has CSF instead.
The scientists noted that this system is particularly active during sleep. In other words, as you sleep your brain cells’ mitochondria remove cellular waste. If you improve your mitochondrial function during sleep, you’ll turbocharge your brain’s maintenance system and get more cleanup done in fewer hours of sleep.
How Being Bulletproof Supercharges Your Brain’s Sewage System
The core practices of the Bulletproof Diet are designed to improve mitochondrial function. In 2013, another team of researchers learned that autophagy is required for healthy brain cell mitochondria.[v] Remember what increases autophagy? That’s right—Bulletproof Intermittent Fasting as well as Protein Fasting. Brain Octane oil also provides ketones, which act as fuel for the mitochondria. If you follow the Bulletproof Diet, you’re already upgrading your brain’s ability to drain waste as you sleep.
By itself, following the Bulletproof Diet Roadmap (get it here free) will help most people get better quality sleep, but sometimes we can all use a little boost. As someone who wants to perform your best, you want to do everything possible to increase cellular energy in the brain while you sleep. Increasing the brain’s efficiency pays dividends during waking hours and even more so during sleep.
There are several ways beyond the basic Bulletproof Diet to improve your sleep, but certain dietary sleep hacks work better for some people than others. This is highly variable, so customize your own ultimate sleep plan by taking this opportunity to be your own biohacker. Don’t try all of the dietary sleep hacks at once because they work in different ways and can counteract each other. Try them out one at a time and see which ones supercharge your sleep.
Lots of my core recommendations may work in part because they influence the way cerebral spinal fluid (CSF) enters the brain’s glymphatic system. For instance:
Yoga and movement (especially inversions!)
Standing instead of sitting at your desk moves more CSF
Using the Bulletproof Vibe
Pranayama and just about any breathing exercises (Art of Living is great for CSF)
Massage and chiropractic care
Hydration
Beyond Food: Supercharge Your Mitochondria to Supercharge Your Brain
I believe that we need sleep (and feel sleepy) when the brain reaches a certain level of toxic protein, and I’ve noticed that just about anything that helps to reduce toxins makes me require less sleep.
Likewise, when you increase mitochondrial function, the Glymphatic system will work better.
It’s no wonder that I need less sleep when I use ketosis or the Unfair Advantage supplement to help mitochondria, or when I eat a low toxin diet and bind excessive toxins with Upgraded Coconut Charcoal, or increase my ability to expel toxins with Glutathione Force.
What’s so great about this field is that new studies keep coming out on how the brain works all the time, so stay tuned for more soon!
More resources to optimize your sleep and supercharge your brain:
The Top Sleep Hacks: The Art and Science of Sleeping
Article: 7 Steps to Bulletproof Sleep
Article: Top 6 Ways to Improve Your Sleep Using Food
Resource Library: All Bulletproof Sleep Hacking Articles and Podcasts
References:
Click to read the complete list of references.
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By Dave Asprey
