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Can apnea cause brain damage?

Thread Status: Hello , There was no answer in this thread for more than 60 days.
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Johan Andersson

Well-Known Member
Jul 1, 2004
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The following is taken from a press release from The American Physiological Society.


Holding Breath for Several Minutes Elevates Marker for Brain Damage
Study Adds to Questions about Whether Free-Diving Is Safe

BETHESDA, Md. (August 4, 2009) — Divers who held their breath for several minutes had elevated levels of a protein that can signal brain damage, according to a new study from the Journal of Applied Physiology. However, the appearance of the protein, S100B, was transient and leaves open the question of whether lengthy apnea (breath-holding) can damage the brain over the long term.

“The results indicate that prolonged, voluntary apnea affects the integrity of the central nervous system, and may have cumulative effects,” the Swedish researchers said. The release of S100B into the blood suggests that holding one’s breath for a long time disrupts the blood-brain barrier, they said.

The concern is that repetitive exposures to severe hypoxia (lowered oxygen supply), such as that experienced by individuals training and competing in static apnea diving events, could cause neurological damage over time. The researchers recommended further research on free divers that would begin early in their careers and follow them for years to monitor their neurological function.

The study is “Increased serum levels of the brain damage marker S100B after apnea in trained breath-hold divers: a study including respiratory and cardiovascular observations.” The researchers are Johan P.A. Andersson, Mats H. Linér and Henrik Jönsson, of Lund University in Sweden. The American Physiological Society published the study.

Breath-hold diving often leads to hypoxia, elevated blood pressure, slowed heartbeat and other physiological changes. However, whether the sport causes any long-term damage to the brain has remained a point of contention. Studies have produced conflicting results.

The authors of this study see cause for concern, noting that in six international competitions between 1998 and 2004, 10% of the contestants in the static apnea events were disqualified after they lost either motor control or consciousness. In this event, participants float face down on the water for as long as possible without coming up for air. The world record for the event is 11 minutes 35 seconds. Divers at international competitions routinely hold their breath 4-7 minutes.

“Whether such hypoxic episodes are associated with a risk for brain damage in these athletes remains to be established,” the researchers said. “Studying the changes in established biochemical markers of brain damage after such performances offers the possibility to address this question.”

Breath hold experiment
Nine competitive breath-hold divers (eight men and one woman) took part in this study, along with six individuals who had limited experience with breath-hold diving. The nine competitive divers formed the experimental group, while the non-divers acted as the controls.

The researchers told the participants to lie on their backs on a cot and hold their breath for as long as possible. The conditions were dry, but mimicked a static apnea dive in which the divers float face down holding their breath. The divers used whatever preparatory techniques they customarily use in competition, such as hyperventilating, insufflation (filling the lungs with as much air as possible) and breath-holding warm-ups.

The researchers took arterial blood samples from a catheter inserted into the artery that runs through the wrist. They took samples before the breath hold, at the end of the breath hold and at fixed intervals for the two hours following the end of the breath hold. The researchers also measured arterial blood gases. They did the same measurements on the individuals in the control group, but the controls rested on their backs for the entire experiment, without performing the breath hold or the warm-ups.

Among the findings of this experiment:

• The average breath-hold time was 5 minutes 35 seconds. The longest was 6 minutes 43 seconds and the shortest was 4 minutes 41 seconds.
• The marker for brain damage, S100B, rose in seven of the nine divers.
• The controls showed no change in S100B
• On average, S100B rose 37% within 10 minutes after the apnea ended.
• S100B levels returned to normal within two hours for all the participants.
• The divers showed signs of asphyxia, that is, blood oxygen levels fell, while carbon dioxide levels rose.

The S100B levels, while elevated, were well below levels associated with brain injury. In brain-injured patients, the presence of S100B in the blood can increase by several hundred percent.

In addition, the elevation of S100B was more transient in the divers, compared to people who suffered brain injury. The divers had a quick return to normal, while S100B levels peak in 24 hours in brain-injured patients.

The transient nature of the increase in S100B among the divers probably indicates the blood-brain barrier has been compromised, allowing the protein to escape from the fluid in the brain into the circulation. The blood-brain barrier controls what passes between the brain and the circulation. S100B would normally remain in the brain.

Other sports have also been associated with a similar transient increase in S100B, the researchers noted, including boxing, headings in soccer, running and long-distance swimming. One study also reported that individuals suffering sleep apnea had elevated levels of S100B in the morning, although another study indicated there had been no change in S100B overnight.

The abstract of the study, with a link to a full text pdf-file, can be found at:
Increased serum levels of the brain damage marker S100B after apnea in trained breath-hold divers: a study including respiratory and cardiovascular observations -- Andersson et al., 10.1152/japplphysiol.91434.2008 -- Journal of Applied Physiology

/Johan
 
Thanks for the info! Although inconclusive, it is nice to see someone studies the topic closer. And I hope more research, including long time monitoring of some freedivers, as suggested in the document, will follow.
 
*drools on keyboard with glazed expression* "whuh?"

Seriously, though, it's an interesting study and I'm glad to see that research is going into this area.
 
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'blood oxygen levels fell, while carbon dioxide levels rose'

Sometimes I wonder about the PHDs that write observations like this.

The biggest scientific crimes ever perpetrated involved the destruction of information by censors, aided and abetted by groups in power. An act by the employees of the State of California was the strangest example that I ever heard of.

My nomination for crime number two is the people doing studies that insist that the information be supplied to them in convenient form at a place of their choosing.

We have hundreds, perhaps thousands of divers, still alive, that played this game for over fifty years. It would be interesting to compare their IQ with a control group. The biggest problem that I can see is the adjusting of scores to correct the fact that diving obviously doesn't attract the brightest bulbs to start with. (You don't have to be crazy, but it helps.)
 
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Other sports have also been associated with a similar transient increase in S100B, the researchers noted, including boxing, headings in soccer, running and long-distance swimming.

Very interesting Johan! I'm curious about the levels of increased S100B in these other sports and how they compare to freediving. Do you have percentages for them? Thanks.
 
'blood oxygen levels fell, while carbon dioxide levels rose'

Sometimes I wonder about the PHDs that write observations like this.

Remember, this was a press release written by a representative of the American Physiological Society for journalists to read. I assume this representative did not expect journalists in general to know the meaning of "asphyxia".


We have hundreds, perhaps thousands of divers, still alive, that played this game for over fifty years. It would be interesting to compare their IQ with a control group. The biggest problem that I can see is the adjusting of scores to correct the fact that diving obviously doesn't attract the brightest bulbs to start with. (You don't have to be crazy, but it helps.)

I agree that there may not be any harm from freediving on your brain, but at the same time I have meet freedivers that have complained about problems with e.g. short-term memory and other cognitive functions. If that related to their freediving background is impossible to say. However, this was one of the original reasons for the study.

I would like to emphasize that the study cannot be used to say that apnea causes brain damage, but at the same time the results indicate that a long apnea affects the integrity of the central nervous system (probably involving an opening of the blood-brain barrier), and do not preclude cumulative effects. This is one of few studies addressing this issue, and further research is definately needed.

Please do not mistake my expressed uncertainty for a condemnation of the sport. However, I believe that whether or not apnea can cause brain damage is an important question that needs to be addressed.

/Johan
 
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Very interesting Johan! I'm curious about the levels of increased S100B in these other sports and how they compare to freediving. Do you have percentages for them? Thanks.

It is somewhat difficult to compare different studies concerning this specific brain damage marker (S100B) because different labs are using different analysis methods that give somewhat differing concentrations. You have to compare your own values to cutoff limits determined by your specific method. Nevertheless, I would say that the increase in S100B that we observed was comparable to those increases observed in boxing, headings in soccer, etc. It should also be noted that the increase in S100B in the present study is well below those reported after, for example, ischemic stroke and hypoxic brain damage after cardiac arrest.

However, it should be taken into consideration that many repetitive exposures to severe hypoxia, each episode not being severe enough to cause any acute noticeable effects, possibly could accumulate damage. At least, we cannot at present rule out that risk.

/Johan
 
Wait a minute. Let's read this carefully...

"Divers who held their breath for several minutes had elevated levels of a protein that can signal brain damage"

It says that the protein signals brain damage. Not causes it.

Does anyone have any more info on the study?
 
"lie on their backs"

Study invalidated.

Of course, I disagree. There may very well be important subjective differences between the immersed and dry condition (when you are used to lying in water it feels different lying on your back and trying a max apnea). However, from what we have seen in previous studies involving both immersed and dry apneas and for the purpose of this study, the physiological differences are unimportant.

/Johan
 
It says that the protein signals brain damage. Not causes it.

That's absolutely right. I hope this will clarify:

1. S100B is a protein normally found in the brain (in the cells and outside of the cells in the extracellular fluid).
2. In the "intact" brain, the blood-brain barrier normally prevents S100B to pass into the circulation (S100B is too big to pass the barrier).
3. If you have a brain damage (from several causes, e.g. trauma, hypoxia, etc.), the blood-brain barrier can be disrupted, allowing S100B to pass from the brain's extracellular fluid into the blood.
4. If the brain damage is severe enough, and in addition to opening the blood-brain barrier also causes cell death, more S100B will enter the blood.
5. Measurments of the S100B concentration in the blood is used to as a tool to indicate the severity of a suspected brain damage (but again, S100B does not cause the damage).

In this study, the increase in S100B was relatively small and transient (within 2 hours, S100B was back to the pre-apnea level). This probably means that the blood-brain barrier was opened, allowing the S100B in the brain's extracellular fluid to pass into the blood. The transient nature of the increase probably means that there were no cell death.

Note that I write "probably". Unfortunately, at the moment that's all we can say. This is just one of the first studies into this topic, and definately not the last.

/Johan
 
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Very interesting article indeed.

Can you explain a little bit more about this opening of the blood-brain barier please.
1. What is the composition/nature of this barrier.
2. What mechanism would explain an opening (or widening , since you mentioned the protein as too big) and closing of the barrier.
3. Are there besides the mentioned "brain damage" as a cause any other theoretical possible mechanismes that could allow this barrier to open op and close again ?

My reason for this question is that i am puzzled by the short recovery of this protein marker to normal values. As we know there are many thing that are triggered by an apnea event that have a transient profile. So could this be another unknown event on the list of 'dive reflexes' that does NOT indicate damage but is for an entire other yet unknown reason. One thing that came to mind as a comparison is the vasodilation/constriction. Could there be a similar harmless effect at work on this barrier, which would completely explain away the transient nature anomaly?
Normally damage to any barrier in the way we think about barriers would only be fixed after some time , in this case some natural repair process.
What is this process and is this fast enough to explain the short transient nature?

Thanks for your answers.



edit: I am not a medic at all so had to do some reading, but after reading up a bit on the internet my theory on the vasodilating effect of the dive reflex also having its effect on the BBB is strenghtened by the following statement (wkipedia) :
Mechanisms for drug targeting in the brain involve going either "through" or "behind" the BBB. Modalities for drug delivery through the BBB entail its disruption by osmotic means, biochemically by the use of vasoactive substances such as bradykinin.

Checking on bradykinin tells me that it is a strong vasodilator............


Has this vasodilation effect (if indeed it is a possible candidate) at all been considered in this study as a possible couse of the protein "leaking" from the area behind the BBB witghout actualy indicating damage ?
 
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As an offshoot, an investigation into the effects of S100B outside of it's normal place (the brain) would be interesting.
 
I'd tell that Glenn raises very valid points, and I tend to believe that he is right that the S100B release is caused by the extreme vasodilatation, and not by dead cells. And it does not necessarily signal any brain damage at all. Another question is what happens afterward - the brain must reproduce the lost S100B, so I wonder what it takes, and what the side-effects are.

It would be also interesting to see differences between valid apneas (without any samba or BO), and the ones finishing with such a failure.

In any case, I am looking forward to hear about more results from the team.
 
The precise mechanism(s) behind the increase in S100B is not established and could involve both neuronal damage and a temporary opening of the blood-brain barrier. The quick and transient nature of the increase probably indicates that it is primarily an opening of the blood-brain barrier that is involved, allowing S100B from the extracellular fluid of the brain to escape into the blood.

As for the mechanisms involved in opening the blood-brain barrier in this condition, they also remain to be established. We attributed the observed increase in S100B to the asphyxia that developed during apnea or to other physiological responses to apnea, for example, the increased blood pressure. If there was a cerebral vasodilation, that could also be involved.

Whatever the reason for the opening of the blood-brain barrier, you should remember that the barrier normally protects your brain, and normally it should not open up.

But again, it is not possible to establish that the observed increase in S100B levels in serum after a maximal-duration apnea reflects a serious injury to the brain.

/Johan
 
It would be also interesting to see differences between valid apneas (without any samba or BO), and the ones finishing with such a failure.

Yes, that would be most interesting. And hopefully we will have some information about that in the near future...

/Johan
 
Ok thanks for your reply.

We have to be very careful with these kind of publication, since before you know it (and this piece is a serious candidate) something gets wrongly interpreted and suddenly freediving causes brain damage (even if only slightly and after prolonged practice).
Also if the opening of the blood-brain barrier is not fully understood you can also not conclude that a temporary opening for yet unknown reasons is bad.
Yes , the barrier is there to protect the brain, but as we have seen so many times in apnea, not all is what it seems.
If I tell you that blood pooling in the lung tissues is bad , you would also normally agree and maybe in a certain situation post this as a serious side effect of freediving. But if you are a freediver at 100m deep it is suddenly good instead of bad. The body has the tendency to protect itself when needed , so maybe his is again another mechanism to protect the brain ???? Who knows. Maybe it is there to positively affect a chemical imbalance caused by apnea.

We have seen this before where medics where sure we would die at a certain depth.....

I applaud these studies , but the way these results where posted full of assumptions (one basic assumption that the presence of these proteins indicates brain damage , even if mildly) is dangerous to our sport.
Together with your statements it is clear that a lot is open to debate or further investigation , but people that read this without your additional info might get a different idea.

I do remember from any scientific experiments I did in the past , that if you want to prove "a" by measuring "b" (if you can not measure "a" directly), you have to first make absolutely clear hat "b" can not be caused by something else or at least put in the paper you publish all the possible other reasons why "b" could be present. This vital piece is clearly missing here.

p.s.
The cold fusion debacle comes to mind as well, where by detecting neutrons coming of of an experiment one wanted to prove that cold fusion took place.
After billions of dollars where spend into fruitless reseach after one such a "successful" experiment, it turned out that the neutrons they detected where generated by a device that was used to insert neutrons in the experiment to provoke this fusion reaction (duhhhhhhhh)
 
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Very interesting topic. Hope that similar research gets the required funding also in the future. Eventually this could also provide the general population new insight on the damage and treatment of drownings and other hypoxia inducing states...

As a subjective note I´ve personally experienced some mild sluggishness after heavy hypoxia training (that has included LMC max. attempts). Not sure though if it´s just normal fatigue from the training. But it stays on for a few days and is quite worrying from time to time...
 
Glenn, I hope (and think) that both the uncertanties and concerns are included the conclusions in the full paper:

"In conclusion, it should be stated that it is not possible to establish that the observed increase in S100B levels in serum after a maximal-duration apnea reflects a serious injury to the brain, although the results raise concerns considering negative, cumulative long-term effects. At the least, the results indicate that prolonged, voluntary apnea affects the integrity of the central nervous system. A long-term follow-up study on individuals at the beginning of their careers as competitive breath-hold divers and after some years of apnea diving would be of great interest in clarifying these issues."

This study is not the final word, it's a piece in a scientific discussion, and hopefully more studies will follow so that this important question can be elucidated. I would have been much less concerned had we not observed any increase in S100B at all. I would be more than happy to see more studies showing that prolonged apnea does not cause brain damage. At the time being I know of only one study suggesting this. But also, that is not the final word, it's a piece in a scientific discussion.

/Johan
 
Johan,

Thanks for the full article. Much appreciated.
I hope, that you don't take any of my remarks as negative but rather productive criticism to your research. The best scientific articles should withstand the flurry of professional criticism or give new insigths to follow up resarch. Then you know you are om the right track
As most freedivers we are very interested and very happy that there are some people that take the time to do some serious research in this still reasonably undiscovered country.
Lets hope this is just one of many more to come.
Maybe one day we will really understand all the intricacies and maybe even ways to prevent possible unwanted side effects of prolonged exposure to our beloved hobby/sport .

p.s. I think the way we are discussing complex stuff here on deeperblue is at least a hint that if there is brain damage, at least it can not be that bad ;-)
On the other hand if i ead some posts .... :crutch :blackeye rofl
 
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