Fascinating, isn't it!? I wrote a post about this over the summer, and there is some evidence that perhaps the Glymphatic System works most efficiently when we are sleeping on our sides.
The reporting that even one night's poor sleep can result in amyloid deposition is sure to stoke fear and catastrophic thinking among those who are troubled by their insomnia, and obsess over the damage they are being told this causes. It's great your article highlighted that the relative risk of dementia is still cumulative, and even with less than 6 hours sleep on average over 25 years, the risk is "only" increased by 20%.
The body knows best. Another study found that naturally we are inclined to sleep more on our sides, likely to facilitate best positioning for the glymphatic system to work, in addition to orthopedic issues, spinal alignment, etc.
The link I posted above also contains a YouTube video showing the blood flow, CSF dishwasher cycle in full effect!
Cheers. I'm glad the Glymphatic System is indeed newly discovered, as I worried that perhaps in medical school I had slept through that lecture ;)
Glymphatics.. the brain mechanism for "flushing"... Fascinating stuff. I wonder if there is something about Long COVID short term memory loss that could be due to something "broken" in this process?
My query is primarily because a very dear friend has this issue... can you point me to any suggested sources for further reading? Regardless, many thanks for your ongoing efforts to enlighten society.
Dr Topol, thanks this article and for including the reference to Ambien. I’ve had anecdotal discussions about it being effective yet not providing the same refreshing sleep one gets without it. Now I have better insights into why.
Are you aware of any therapeutics being developed specifically to enhance NREM and/or deep sleep? Also, in addition to other modalities, monitoring seems the best way improve NREM. There are a number of devices capable of non-invasively monitoring sleep stages including Oura, AppleWatch, Garmin, etc.
Thanks very much for this. Below: vitamin D, helminthic therapy and whole-body vibratory "exercise".
Vitamin D supplementation, in quantities greater than recommended by governments and many doctors, is needed to reduce the risks of neurodegeneration -> dementia. For average weight adults, 0.125 milligrams supplemental vitamin D3 cholecalciferol (125 micrograms = 5000 IU) is needed, on average, per day, to attain the 50 ng/mL (125 nmol/L = 1 part in 20,000,000 by mass) level of 25-hydroxyvitamin D in the bloodstream which the immune system needs to function properly. Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/.
The very small daily vitamin D3 supplemental intake quantities recommended by governments and many doctors for adults - such as 0.025 milligrams (25 micrograms = 1000 IU) - are only sufficient to attain the 20 ng/mL (50 nmol/L = 1 part in 50,000,000 by mass) level of circulating 25-hydroxyvitamin D which the kidneys need to properly regulate calcium-phosphate-bone metabolism. Without proper vitamin D3 supplementation or recent months of extensive ultraviolet B skin exposure, most people have half or less of this: 10 to 25 ng/mL.
There's very little vitamin D3/2 in food, fortified or not - and.fortified food often uses the less effective, unnatural, D2 form. UV-B skin exposure of ideally white skin is not naturally available to most people all year round. It always damages DNA and so raises the risk of skin cancer.
Proper vitamin D3 supplementation is needed to reduce the risk of neurodegeneration - Alzheimer's disease, Parkinson's disease, multiple system atrophy, dementia with Lewy bodies etc. - https://vitamindstopscovid.info/00-evi/#3.3.
It is not widely appreciated, but the proclivity of humans (and our companion and agricultural animals) to self-destructive inflammatory responses is due not just to inadequate circulating 25-hydroxyvitamin D (needed by many types of immune cell for their intracrine - inside each cell - signaling systems) but also due to our _lack_ of helminths (intestinal worms): : https:// vitamindstopscovid.info/06-adv/.
Helminths emit compounds which downmodulate the host's inflammatory - indiscriminate cell destroying - immune responses, which target them. The hosts, including our ancestors, evolved overly-aggressive inflammatory immune responses to counter the downmodulation inherent in ubiquitous helminth infections. Now most of us (the exceptions are in Africa and other developing countries) are de-wormed, our inflammatory responses are in general overly- aggressive. Some people, due to genetic variations and perhaps exposure to particular antigens, have particularly strong, and so self-destructive, inflammatory immune responses leading to numerous severe conditions, including asthma, psoriasis, rheumatoid arthritis, Crohn's disease and cluster headaches / migraine.
The above-mentioned page cites and discusses research which shows that two very different lines of treatment are effective against the same broad set of inflammatory auto-immune diseases, which are generally considered incurable by mainstream medicine.
The first is artificially high levels of 25-hydroxyvitamin D, attained through much higher levels of vitamin D3 supplementation than is required to attain the 50 ng/mL circulating level of 25-hydroxyvitamin D the immune system needs to function properly. This is the Coimbra protocol - and essentially the same protocol of Peter Batcheller is highly effective at suppressing cluster headaches and migraine.
I suggest that this high level of 25-hydroxyvitamin D somewhat activates "vitamin D receptors" (really the calcitriol receptors) in Th1 regulatory lymphocytes, which reduces their ability to produce pro-inflammatory cytokines in their initial, pro-inflammatory, startup program. See my summary of the research on Th1 intracrine (they called it "autocrine" which is not quite right) signaling carried out by Chauss et al. at: https://aminotheory.com/cv19/icu/#2021-Chauss.
The second type of treatment is helminthic therapy https://helminthictherapywiki.org - introducing relatively benign helminths so that the compounds they exude reduce the overall ability of the immune system to mount these self-destructive, indiscriminate cell destroying immune responses.
As far as I know, no vitamin D researchers take an interest in helminthic therapy and the people researching helminths and their compounds take no interest in vitamin D research.
Few vitamin D researchers and almost no immunologists understand the crucial role of 25-hydroxyvitamin D -> calcitriol intracrine (inside each cell) and paracrine (to nearby cells, typically of different types) in the ability of many types of immune cell to respond to their changing circumstances. There are no peer-reviewed tutorials on these signaling systems, which are also used by cell types which are not related to the immune system. I wrote a tutorial in late 2020: https://vitamindstopscovid.info/02-intracrine/.
Another angle on clearing debris from the brain is that ordinary exercise and a particular form of vibratory exercise, which does not involve exertion, are known - or at least thought to - reduce depression.
If depression is in large part caused by lack of neurogenesis in the hippocampus (there is lots of evidence for this) and if this is hindered by inflammatory immune responses and/or the buildup of waste products there, it would not be surprising if the increased blood flow and/or the physical vibration of ordinary exercise would clear out more of these waste products.
The particular form of non-exertion "exercise" involves tensing the muscles and standing on a robustly engineered motorised platform which vibrates the entire body: Google search for: "whole body vibration". This too would physically vibrate the brain and so stimulate the clearance of waste products, even though it probably does not much alter blood flow.
Thank you so much for this. The idea of waste clearance makes sense intuitively, and here you offer science that backs this up. This is, for me, an area of particular concern. Anecdotally, I know of all too many women my age and older who have difficulties with sleep. In my own experience, it is abundantly apparent how much difference a decent night’s sleeps means, and also how much drugs like Ambien/Zolpidem are highly problematic.
So, I applaud you, yet once again, for sounding the alarm on this problem. As you note, “With the new elucidation of this pivotal drainage mechanism, it is notable that none of the commonly used sleep medications or supplements have been shown to improve waste clearance, the principal function of sleep. Or promote deep slow- wave sleep without important side effects. We are in desperate need for effective and safe sleep medications that will achieve these objectives.”
What I worry about is that, in this age of ever-expanding high tech medicine, few will care about these basic needs, which is what makes your voice all the more important.
I have never needed a fully dark bedroom to fall asleep. I'm 76 but rarely have trouble sleeping. I do take CBD at night. My brain is still fine. I still have a job.
Fascinating, isn't it!? I wrote a post about this over the summer, and there is some evidence that perhaps the Glymphatic System works most efficiently when we are sleeping on our sides.
https://mccormickmd.substack.com/p/is-there-a-better-head-position-for
The reporting that even one night's poor sleep can result in amyloid deposition is sure to stoke fear and catastrophic thinking among those who are troubled by their insomnia, and obsess over the damage they are being told this causes. It's great your article highlighted that the relative risk of dementia is still cumulative, and even with less than 6 hours sleep on average over 25 years, the risk is "only" increased by 20%.
The body knows best. Another study found that naturally we are inclined to sleep more on our sides, likely to facilitate best positioning for the glymphatic system to work, in addition to orthopedic issues, spinal alignment, etc.
The link I posted above also contains a YouTube video showing the blood flow, CSF dishwasher cycle in full effect!
Cheers. I'm glad the Glymphatic System is indeed newly discovered, as I worried that perhaps in medical school I had slept through that lecture ;)
Glymphatics.. the brain mechanism for "flushing"... Fascinating stuff. I wonder if there is something about Long COVID short term memory loss that could be due to something "broken" in this process?
Thanks....certainly possible
My query is primarily because a very dear friend has this issue... can you point me to any suggested sources for further reading? Regardless, many thanks for your ongoing efforts to enlighten society.
I find that a banana before bedtime helps (magnesium, potassium, tryptophan and all that).
Since I have abnormally high potassium, my doctor has forbidden me to eat bananas.
Yes, well, I wasn't advocating that everyone should do this.
Dr Topol, thanks this article and for including the reference to Ambien. I’ve had anecdotal discussions about it being effective yet not providing the same refreshing sleep one gets without it. Now I have better insights into why.
Are you aware of any therapeutics being developed specifically to enhance NREM and/or deep sleep? Also, in addition to other modalities, monitoring seems the best way improve NREM. There are a number of devices capable of non-invasively monitoring sleep stages including Oura, AppleWatch, Garmin, etc.
Thanks very much for this. Below: vitamin D, helminthic therapy and whole-body vibratory "exercise".
Vitamin D supplementation, in quantities greater than recommended by governments and many doctors, is needed to reduce the risks of neurodegeneration -> dementia. For average weight adults, 0.125 milligrams supplemental vitamin D3 cholecalciferol (125 micrograms = 5000 IU) is needed, on average, per day, to attain the 50 ng/mL (125 nmol/L = 1 part in 20,000,000 by mass) level of 25-hydroxyvitamin D in the bloodstream which the immune system needs to function properly. Please see the research cited and discussed at: https://vitamindstopscovid.info/00-evi/.
The very small daily vitamin D3 supplemental intake quantities recommended by governments and many doctors for adults - such as 0.025 milligrams (25 micrograms = 1000 IU) - are only sufficient to attain the 20 ng/mL (50 nmol/L = 1 part in 50,000,000 by mass) level of circulating 25-hydroxyvitamin D which the kidneys need to properly regulate calcium-phosphate-bone metabolism. Without proper vitamin D3 supplementation or recent months of extensive ultraviolet B skin exposure, most people have half or less of this: 10 to 25 ng/mL.
There's very little vitamin D3/2 in food, fortified or not - and.fortified food often uses the less effective, unnatural, D2 form. UV-B skin exposure of ideally white skin is not naturally available to most people all year round. It always damages DNA and so raises the risk of skin cancer.
Proper vitamin D3 supplementation is needed to reduce the risk of neurodegeneration - Alzheimer's disease, Parkinson's disease, multiple system atrophy, dementia with Lewy bodies etc. - https://vitamindstopscovid.info/00-evi/#3.3.
It is not widely appreciated, but the proclivity of humans (and our companion and agricultural animals) to self-destructive inflammatory responses is due not just to inadequate circulating 25-hydroxyvitamin D (needed by many types of immune cell for their intracrine - inside each cell - signaling systems) but also due to our _lack_ of helminths (intestinal worms): : https:// vitamindstopscovid.info/06-adv/.
Helminths emit compounds which downmodulate the host's inflammatory - indiscriminate cell destroying - immune responses, which target them. The hosts, including our ancestors, evolved overly-aggressive inflammatory immune responses to counter the downmodulation inherent in ubiquitous helminth infections. Now most of us (the exceptions are in Africa and other developing countries) are de-wormed, our inflammatory responses are in general overly- aggressive. Some people, due to genetic variations and perhaps exposure to particular antigens, have particularly strong, and so self-destructive, inflammatory immune responses leading to numerous severe conditions, including asthma, psoriasis, rheumatoid arthritis, Crohn's disease and cluster headaches / migraine.
The above-mentioned page cites and discusses research which shows that two very different lines of treatment are effective against the same broad set of inflammatory auto-immune diseases, which are generally considered incurable by mainstream medicine.
The first is artificially high levels of 25-hydroxyvitamin D, attained through much higher levels of vitamin D3 supplementation than is required to attain the 50 ng/mL circulating level of 25-hydroxyvitamin D the immune system needs to function properly. This is the Coimbra protocol - and essentially the same protocol of Peter Batcheller is highly effective at suppressing cluster headaches and migraine.
I suggest that this high level of 25-hydroxyvitamin D somewhat activates "vitamin D receptors" (really the calcitriol receptors) in Th1 regulatory lymphocytes, which reduces their ability to produce pro-inflammatory cytokines in their initial, pro-inflammatory, startup program. See my summary of the research on Th1 intracrine (they called it "autocrine" which is not quite right) signaling carried out by Chauss et al. at: https://aminotheory.com/cv19/icu/#2021-Chauss.
The second type of treatment is helminthic therapy https://helminthictherapywiki.org - introducing relatively benign helminths so that the compounds they exude reduce the overall ability of the immune system to mount these self-destructive, indiscriminate cell destroying immune responses.
As far as I know, no vitamin D researchers take an interest in helminthic therapy and the people researching helminths and their compounds take no interest in vitamin D research.
Few vitamin D researchers and almost no immunologists understand the crucial role of 25-hydroxyvitamin D -> calcitriol intracrine (inside each cell) and paracrine (to nearby cells, typically of different types) in the ability of many types of immune cell to respond to their changing circumstances. There are no peer-reviewed tutorials on these signaling systems, which are also used by cell types which are not related to the immune system. I wrote a tutorial in late 2020: https://vitamindstopscovid.info/02-intracrine/.
Another angle on clearing debris from the brain is that ordinary exercise and a particular form of vibratory exercise, which does not involve exertion, are known - or at least thought to - reduce depression.
If depression is in large part caused by lack of neurogenesis in the hippocampus (there is lots of evidence for this) and if this is hindered by inflammatory immune responses and/or the buildup of waste products there, it would not be surprising if the increased blood flow and/or the physical vibration of ordinary exercise would clear out more of these waste products.
The particular form of non-exertion "exercise" involves tensing the muscles and standing on a robustly engineered motorised platform which vibrates the entire body: Google search for: "whole body vibration". This too would physically vibrate the brain and so stimulate the clearance of waste products, even though it probably does not much alter blood flow.
Thank you so much for this. The idea of waste clearance makes sense intuitively, and here you offer science that backs this up. This is, for me, an area of particular concern. Anecdotally, I know of all too many women my age and older who have difficulties with sleep. In my own experience, it is abundantly apparent how much difference a decent night’s sleeps means, and also how much drugs like Ambien/Zolpidem are highly problematic.
So, I applaud you, yet once again, for sounding the alarm on this problem. As you note, “With the new elucidation of this pivotal drainage mechanism, it is notable that none of the commonly used sleep medications or supplements have been shown to improve waste clearance, the principal function of sleep. Or promote deep slow- wave sleep without important side effects. We are in desperate need for effective and safe sleep medications that will achieve these objectives.”
What I worry about is that, in this age of ever-expanding high tech medicine, few will care about these basic needs, which is what makes your voice all the more important.
I have never needed a fully dark bedroom to fall asleep. I'm 76 but rarely have trouble sleeping. I do take CBD at night. My brain is still fine. I still have a job.