Sleep and brain detoxification

In this article Dr. Agnese Mariotti resumes the results of a recent research showing that sleep has an important detoxifying effect on our brain. This is an encouraging finding and supports the essential role that naturopathy (as well as other alternative medicines) gives to high quality sleep in order for the body to clear toxins from liquids and tissues, stay healthy and recharge itself during the night.

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Beauty sleep: giving our brain a detox

How sleeping flushes our brain clear of toxins.

Author: Agnese Mariotti

“We all need our regular beauty sleep, but how exactly does sleep produce its regenerative effects? Scientists have uncovered a mechanism by which sleep helps eliminate toxic substances from the brain and thus critically contributes to maintaining our good health.

As opposed to the brain, the body’s waste products are eliminated by the lymphatic system, a network of vessels that transfer metabolites from the tissues to the blood circulation and finally to the liver where they are degraded. The brain lacks lymphatic vessels and must rely on other mechanisms to get rid of toxins.

Nedergaard and colleagues of Rochester University recently discovered that the main detoxifying system in the brain consists of the cerebrospinal fluid (CSF) that is produced by filtration through the brain arteries into the surrounding spaces, and circulates among the brain structures.

Why we need a detox

The CSF moves by convective flow into the brain parenchyma and comes in contact with the interstitial fluid (ISF) present between cells in the so-called interstitial space, thus exchanging solutes with it. In particular, the CSF collects metabolites that were released in the ISF during brain activity, and transports them away from the brain to the venous blood circulation, for delivery to the liver.

There is evidence that in some neurodegenerative diseases and in brain injuries in which high amounts of “toxins” are produced, the CSF cannot efficiently clear the brain, which causes accumulation of toxins and further brain damage.

So, would it be possible to increase metabolites clearance from the ISF and improve our brain –and consequently general– health by enhancing CSF circulation? Nedergaard’s team has found that sleep does exactly this.

Flushing the brain

The scientists monitored CSF circulation in mice by injecting fluorescent dyes in the animals’ brains and followed their distribution using two-photon imaging. They found that a green dye administered to mice while sleeping diffused in the brain much more extensively than a red dye injected in the same mice after they were awaken.

The different dye distribution was the result of increased CSF influx and circulation into the brain of sleeping mice. This was caused by a significant increase (over 60%) in the volume of the interstitial space during sleep that led to decreased resistance to fluid movements and facilitated CSF flow.

As a consequence of increased CSF flow, toxic metabolites such as beta-amyloid, a protein degradation product that accumulates in the brain causing Alzheimer’s disease, were cleared much more efficiently from mice brains during sleep.

The scientists then demonstrated that sleep is accompanied by a decreased release in the brain of some neuromodulators, such as noradrenergic mediators, that sustain brain activity in the awake state. These neurotransmitters also regulate cell volume and specifically induce an increase in cell size during the awake state, which is followed by a reduction in the interstitial space.

Therefore sleep, by reducing the concentration of these neuromodulators decreases cell volume and increases the interstitial space, thus promoting CSF circulation and metabolite clearance.

Medical benefits

What are the implications of these findings? The study suggests that insufficient sleep —but also stress that increases the levels of noradrenergic transmitters— may contribute to neurodegenerative diseases by inducing a state of metabolic intoxication. We can thus envisage drugs that can mimic the effects of sleep at the molecular level and improve CSF circulation and metabolite elimination.

In addition, preclinical studies have shown that it’s possible to monitor CSF circulation in animals by Magnetic Resonance Imaging. This analysis applied to human patients could help diagnose neurodegenerative diseases at their initial stages when the CSF flux may already be reduced, and promptly administer therapies.

In conclusion, this study is the first demonstration of the detoxifying function of sleep and suggests that we really need to spend about a third of our lives sleeping in order to live healthily the other two thirds.”


Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, & Nedergaard M (2013). Sleep drives metabolite clearance from the adult brain. Science (New York, N.Y.), 342 (6156), 373-7 PMID: 24136970.