Widespread drastic reduction of brain myelin upon prolonged endurance exercise | Hacker News Reader

Widespread drastic reduction of brain myelin upon prolonged endurance exercise

biorxiv.org

101 pointsanigbrowl60 comments

People who engage in ultra running - that extends beyond 24 hours- often find their limits in hallucination before their body just won’t run any further. I suspect you will find a similar effect with extended sleep depravation.

As an ex-ultra runner I can attest to this, but they are usually awesome. However, I did notice that the more races/backyard races/years of training reduced the feelings of mind fog and wild hallucinations dramatically and recovery time decreased. This was the case with the group members I trained with as well. So, it would be interesting to know if the study included veterans or newcomers, or how many marathons the participants had under their belt.

Did you ever experience feelings or have thoughts that were overwhelmingly lovely? Like only you can see the true beauty of the path you are on? I dabble in combining sleep deprivation with multi day fasting. Dream processes start to kick in, and sometimes the copying from the brain’s 1 day RAM to the brain’s long storage happens while awake. This process is only supposed to happen during REM sleep, but when it happens in awake real-time it feels like a spiritual experience. You look at a bird and all the sudden that bird is integrated with all prior knowledge in a way that makes it feel like a religious vision. This brain race condition feels like being one with the great spirit or something.

Unfortunately not. It's a very strange feeling. You are awake but your brain is so depleted that you can't make sense, you see things that you would normally know would not be real but because you are so out of it you don't realize for a couple minutes that trees really can't talk. I have heard of other runners who have very spriritual experiences though.

I've done marathons and numerous sleep deprivation/caloric deprevation events and never got to hallucinations, only micro-naps which, on occasion, resulted in my waking up with a mouthful of gravel.

...So whats your tip to achieving these awesome hallucinations, and how do I get there! ;-)

don't fall asleep. You don't even need to run to achieve them -- about 42 hours should be enough to experience them without any exercise at all. The only trick is every time you get tired -- push through it and wake yourself up with movement or music. After pushing through the exhaustion you'll get a 'second wind' of awareness -- and a third and so on, as those later exhaustions occur.

The goal isn't to be at 100% awareness during these moments -- it's to not micro-nap and relieve the lack of sleep.

I remember once playing a game of go with a friend after 40 hours of no sleep (drug-free), and seeing purple electricity radiating across the stones and outlining the boundaries of their activities against one another. Walking down the hallway I experienced that recession of reality like when Frodo first encounters the Nazgûl in the forest and the path pulls away from him.

Lack of sleep is incredibly psychedelic. Take this from someone who has done many -- and good luck ;)

What's the long term sequences of this body abuse?

24 hours of running, crappy nutrition, really just completely depleted, and keep going. lol.

> I suspect you will find a similar effect with extended sleep depravation.

Early into my investment banking career, I once worked about 130 hours in a single week and started hallucinating in the office, hearing voices as if my relatives were speaking random sentences to me

Sample size of one, but I can definitely attest to the effect

That's nuts. I had to do 100-hour weeks a few times in my career, and felt that any time above that had zero or even negative productivity.

Is it really necessary to do so many slide decks in order for IB to be as productive?

That was basically my worst experience ever over the course of 7 years and I have never personally met anyone who's worked more ours in one week (lol?) but yeah, any "meaty" meeting is likely to generate a few hundred slides if you include all of the revisions, so it gets out of hand fast. I probably had 5-10 100-hour weeks in any given year, but 70-80 hour weeks would be pretty normal. (I probably also had 4-5 40-hour weeks in any given year, but you usually everyone keeps those on the DL...)

Shit compounds when there's a deadweight on the team, or a managing director that doesn't know what they want / has poor planning, or everyone's busy on other projects or the situation is actually complex. In that particular case, it was a combination of a deadweight analyst on a very lean team (I was the only associate, no VP, one very senior director trying to make MD and 2 other super senior MDs... for a $2B M&A deal), poor planning and an actually complex situation (crossborder, post-bankruptcy former public company with public debt still outstanding, multiple tax jurisdictions, CFIUS issues, you name it) leading up to a board meeting on Friday (to which I took a flight to deliver the books, which added to the hours...)

I'm from Texas but went to college in Michigan. I used to sometimes drive it straight through (20 hours, with stops every 6 hours for fuel, food and toilet). The times I'd stop were because I'd start hallucinating, not because I couldn't stay awake. Was always super annoying having to stop since I'd invariably be 1-2 hours from my parents place.

I’m super curious. Can you explain what you mean by hallucinations?

Normally I'd have the sense that I was seeing things in my periphery that weren't there. It was almost like having the fear that a deer was running into the road, except the deer was never there. It was distracting enough to be dangerous.

At 20 hours? I used to do that regularly. Wake up at 6 am, work, party til 2 am on a Friday. I've never heard of anyone hallucinating in that short of a time. That only happens when you're up for like 3 days straight.

> “I've never heard of anyone hallucinating in that short of a time.”

Did you… read the comment you’re replying to? Or just skip straight to writing the one-upper reply?

Staring at the road, especially at night, for that long doesn't help. I drove 16ish hours from Denver to Fargo with minimal breaks recently. Got to Jamestown, ND (not far from Fargo) and had to pull over because it was starting to get weird.

> I've never heard of anyone hallucinating in that short of a time.

Do you mean besides intentionally because of the effects of drugs and/or alcohol?

(Before people come for me: I’m not saying alcohol causes hallucinations, more that it affects perception and makes it very difficult to figure out if you’re tired enough to hallucinate)

Driving requires constant mental engagement. I find driving for 8 hours to be more tiring than a day of work.

N=4,

"Donostia city marathon 2022 (n=2), and the Zegama-Aizkorri mountain marathon 2023 (n=2). All of them were well-trained men aged 45-73 years old completed the marathon in a good healthy state."

mountain marathon had 5400+m of elevation gain. Yikes.

The 73 year old is doing well for his age. No idea about the mountain marathon times (unless the 73 year old ran the mountain marathon - mountain or urban, 3:45 is a good time regardless for a 73 year old)

Table S3 from paper

                    Runner 1    Runner 2    Runner 3     Runner 4
    Age             73          59          45           46
    Weight(kg)      58          76          69           71
    Height(cm)      160         181         180          180
    Time            3h45m       3h59m       4h40m        6h06m
    HR (avg)        150         145         152          N/A

Near the end of the paper:

    Though the risk rise (26% higher) is low in individuals with a history of vigorous physical activity, there is a five-fold mortality rate increase in professional athletes (39). Vigorous physical activity likely increases glutamate excitotoxicity and oxidative stress, hastening neurodegeneration in individuals with a genetic predisposition for the development of ALS (38). Therefore, while the impact of marathon running in well trained individuals is null, for those with ALS genetic risk, disease vulnerable motor areas are impacted more on otherwise physiological myelin expenditure (e.g., corticospinal tract), as myelin itself and myelin-producing oligodendrocytes are also vulnerable to glutamate excitotoxicity as well (40).

Not just ALS: glutamate excitotoxicity is one of the proposed mechanisms for progressive forms of multiple sclerosis

I've done a number of Ironmans and marathons. I definitely feel "punch drunk" for a couple days after doing Ironman class races and the main training days (think like 100 mile bike / 10 mile run in one session).

But I completely recover after a day or two.

I personally draw the line at sleep deprivation, so those nutso Barkley Marathoners that go like 3 days without rest? Nah. RAAM? Nope. No thatnks.

Training is very good for the body but actual all-out racing happens at a level of exertion that typically isn't. Your body recovers from it, but at the Ironman distance it takes longer than people often think. Athletes show elevated muscle damage and inflammation biomarkers up to three weeks after a race. A lot of the fatigue is actually central nervous system fatigue, which gives the brain fog.

For those who haven't heard of the Barkley before, there's a fantastic documentary about it. Apparently it's on Amazon Prime now.

https://barkleymovie.com/

The Barkley Marathons: The Race that Eats Its Young

If you apply to join and are accepted, the acceptance letter begins with something like, "Deepest condolences, you have been accepted..."

I've made the mistake of driving home (to Philly) the day after IM Lake Placid the first time I raced it.

It's bad for a number of reasons, but the punch-drunk feeling was unexpected.

I made sure to stay an extra few days when I did it again.

The only time I hallucinated was after a single-day double crossing of the Grand Canyon, a 15-hour run/hike iirc. I would see a random tetris game in front of me even though I never played.

Sleep deprivation in my experience can produce similar effects.

It feels like a wakeful dream. Where despite having open eyes and even interacting with the world on some level, the brain is off watching an entirely different movie.

Totally true for me too. I remember the days after college all nighters always seemed to have a strange quality.

I had a similar experience on a big multi-peak one day traverse. It was unusually hot/humid and turned into an 18 hour sufferfest. Thankfully I wasn’t the one driving afterwards, as I was hallucinating shadowy people standing in every open space along the side of the road.

Interestingly, I’ve done a few similar hikes and had plenty of energy after to cook a big pot of chili at our basecamp and enjoy a couple of beers. Exhaustion is weird.

Was it more like you just had a vivid mental image of it, or was it like clear and convinced it was there and tangible?

It was definitely vivid. I can't say that I was convinced it was there because tetris blocks do not appear in nature, so I obv knew it was a hallucination.

Running short distances is definitely good for health, but marathon running is hugely detrimental from any aspect. Running itself is a stressor and stress is good only in small quantity and when it's not chronic! In fact, you ruin the benefits of exercise if you counter the stress with antioxidants, etc. Running for hours is only good for the ego!

Citations needed on this. Overtraining is well documented and detrimental to many things, but most research indicates a linear relationship between overall cardiovascular fitness and just about every measurable health outcome. It’s absolutely possible to train at the volumes and distances necessary for the marathon without overtraining.

https://peterattiamd.com/how-does-vo2-max-correlate-with-lon...

It's not like I need to record or remember all studies I've read; I put an effort at remembering the conclusions, and some of the rationale, but here's one article for you: [0]

There's a lower and a upper limit for any health intervention. Too little, or too much of the good thing could be equally detrimental. This literally applies to anything - water, minerals, vitamins, food, sleep duration. HIIT has benefits without doubt, so does sprinting and moderate-distance running, but beyond that, it's just a terrible way to spend the limited seconds of your life!

Also, we have cartilage, which, as far as I know, cannot be regenerated. There are some stem cell and microneedle approaches, but nothing proven to be working yet.

In addition, you need to consume more carbs for distance running, and that definitely leads to accelerated aging.

Which species live longer - the cheetah or the turtle? Speeding up metabolism means reaching faster the Heyflick limit.

If you look at the findings of the Longevity Project [1], those with the longest lifespan are scientists, not sports people, and definitely not lawyers or salespeople, which had the shortest.

[0]: https://www.cbsnews.com/news/too-much-running-tied-to-shorte...

[1]: https://en.wikipedia.org/wiki/The_Longevity_Project

Do you have any evidence that supports this? Twenty years of running anecdotally strongly suggests otherwise, but I’m open to an actual study.

Running or marathon running?

Both.

Skip the marathons - they only boost your ego at the expense of your lifespan... as, in addition, you waste productive life... just runing.

So is that a bad thing? It says it recovered but I imagine during the meantime having less myelin would affect brain function.

Decrease in myelin layers around neurons are what causes MS if I'm not mistaken. It's essentially the insulation so that the electric signal does not travel in an unwanted way. I'd imagine myelin having a similar function in the brain, so there might be some signal crossing that is not supposed to happen?

I don't have a source handy, but believe that MS is hypothesized to be caused by the immune system attacking the myelin sheathing (autoimmune disease), so it is quite a different process.

Not sure but it seems bad to me.

Could it lead to increased plasticity and also have benefits?

Why does it seem bad? Less of something doesn't necessarily mean its bad.

Perhaps the brain is simply making use of extraneous matter for energy or its purging out unnecessary neurons. Maybe it decreases creativity, but increases arithmetic ability.

My entire point is we have no idea what the end results are, just because there's a reduction doesn't necessarily indicate a problem.

> Why does it seem bad? Less of something doesn't necessarily mean its bad.

Myelin is pretty damn important for the brain's function. Signals go much, MUCH slower without myelin, and there are a number of clinical disease and problems that can happen thereof. One of the main effects of B12 deficiency is loss of the myelin sheath around the optic nerve causing blindness, and the psychiatric effects of losing myelin in the brain -- in addition there are a lot of disorders where a primary effect is myelin degradation / loss. It's been very well studied.

Depleting your fridge is not the same as permanently destroying it.

B12 deficiency doesn't permanently destroy it either. It's just the body cannot produce myelin, and if that happens for a long enough period of time, the nervous system is exposed to damage that is permanent, even after the body can regenerate the myelin

My shallow understanding is that myelin improves neurons' connectivity, so the decrease of it would imply degrading performance in neural activities?

Also, the myelination process happens when you learn new things, so it might be interesting to analyze how the recovery period might be exploited to facilitate learning.

Would love to hear brain scientists thoughts.

or is it like body fat but for brain cells?

I would be very interested to see if the same effect holds in those athletes who maintain a low carbohydrate diet.

Maybe if the body is adapted to use fat as the primary energy source from the get-go, it would not go looking for energy in such a seemingly strange place.

Not just lost, but used as an energy reserve?

A 2012 study in mice found glial-produced myelin supplying energy to neurons as lactate after mitochondrial respiration was inhibited (like an proposed astro-glial shuttle for some glutamatergic neurons).

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613737/

    once myelination has occurred, reduced mitochondrial functions do not 
    perturb oligodendrocyte survival, myelin maintenance or axonal integrity.

    We proposed that oligodendrocytes survive by enhanced glycolysis, and 
    predicted to see in vivo an increase in the brain lactate concentration 
    using localized proton magnetic resonance spectroscopy (MRS). As expected,
    Cox10 mutants showed a more strongly increased lactate resonance

    lactate is not cleared by drainage, but is locally metabolized

    the monocarboxylate transporter MCT2 localizes to myelinated axons. 
    This strongly suggests that lactate generated in oligodendrocytes 
    is released and reaches the axonal compartment

    Our model of axon–oligodendrocyte metabolic coupling is reminiscent 
    of the astroglial ‘lactate shuttle’, which is thought to support 
    the energy metabolism of glutamatergic synapses in the cortex

So wow - myelin lipids used as an energy reserve if not buffer.

It makes a lot of sense that glial cells hard at work building structure and metabolites for neurons might also provide energy. Indeed, perhaps the energy benefit was the initial evolutionary advantage, and then insulation enabling longer neuron runs (and lower energy use) would permit other adaptations.

(Also, for those extolling fatigue hallucinations or psycho-active breath-holding, please remember that's toxic to neurons, and neuronal regeneration is ... limited.)

If this is a serious problem we should have seen plenty of evidence of cognitive problems among endurance athletes.

Plenty of amateur cyclists expend equivalent amounts of energy to a marathon on training rides each and every weekend.

They might get sufficient amount of B vitamins to replenish myelin. Maybe when you gave them food without those you'd see a lasting damage?

another case of too much of a good thing can be bad?

For sure you can’t do anything too much, even too much air/water is dangerous

Megadose B1/B5/B6/B12 when doing endurance exercises? Those should promote remyelination.

It makes no evolutionary sense to reduce nerve conductivity and thus function when attempting to flee or migrate in a situation when carbs are scarce.

Further, keto/VLC diets are neuroprotective.

Highly skeptical.

Disclaimer: I didn't read more than the first page of the paper

But there are lots of possibilities, right? For instance, if the alternative is glia starvation, and the myelin can be later regenerated, that might be preferable to glial death.

Separately, it's been theorized that myelin first evolved as an energy storage. It may respond to the same biological processes that cause adipose tissue to release fatty acids.

Further disclaimer: I don't really know what I'm talking about, but it seems like there are lots of possibilities why this observed result might have an evolutionary purpose, or explanation.

do you have any citations for the myelin evolution as energy storage? That's a fascinating take.

Do you think every acute reaction in the body to intense exercise has to make "evolutionary sense"? Do shin splints make evolutionary sense?

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