Queensland Government: Gold Coast researchers make chronic fatigue breakthrough

[melihtas]

Their findings don't seem to match with what Stanford is seeing. According to Ron Davies the problem is in the serum, not the cells.

Maybe the "thing" in the serum is causing the receptors dysfunctioning and nothing wrong with them structurally. Griffith team should repeat the tests with ME/CFS cells in healthy serum.

 

[slysaint]

In the meantime, the research is a stark reminder of how serious CFS/ME can be - and how useless, and potentially even damaging, current treatment options are.

In my opinion, until there is a definitive discovery the more this message gets out there the better.

 

[A.B.]

Interesting that the TRPM3 ion channels are closely linked to glucose metabolism (ie energy).

I've been saying for a while that there seems to be a problem with glucose metabolism due to patient reports of reactive hypoglycemia, hypoglycemia like episodes but without actual low blood sugar, poor fasting tollerance, the beneficial effect of small frequent meals. I thought this was only in a subgroup but research of the last few years continues to find abnormalities in this area, so maybe this is a key feature of the illness after all.

I reached a blood sugar level of 43 mg/dL during a 4(?) hour glucose tollerance test, yet an in depth endocrinological investigation revealed no identifiable illness.

I also have substantially reduced VO2max in a CPET (about 40% of expected, too low to be explained by a sedentary lifestyle) which is consistent with impaired aerobic energy production.

Fluge and Mella found an impaired ability to utilise glucose in the efficient aerobic energy production pathway. There are signs that other problems with energy generation also exist.

 

[Snow Leopard]

I appreciate the positive coverage, but well, unless they actually have a "breakthrough" diagnostic test, all of this is hype and speculation.

 

[Jenny TipsforME]

In fact, the two most commonly prescribed treatments for the condition are cognitive behavioural therapy and exercise, neither of which have any evidence to support they work - and many feel could actually be doing more harm than good

"The new research also suggests that diagnosing exercise is just unbelievably bad as it can put the body under further stress," he added.

Good to get this message circulating the globe at least! I also have reservations about a future bite, but in the meantime if new patients, friends and family read this it could prevent harm.

 

[Jenny TipsforME]

class of receptors TRPM3 belongs to are also known as 'threat rececptors', because they're upregulated when the body is under any kind of threat, such as infection, trauma, or even childbirth.

This interests me as an hypothesis. Could it be a sort of missing link?

1) Genetic susceptibility
2) many types of possible enviro trigger stressors: mono, enterovirus, injury etc
3) faulty TRPM3 receptors perceive serious ongoing threat (even if virus etc eradicated)
4) body goes into downregulated dauer state to avoid serious threat and creates lots of metabolic abnormalities

What do you think? Brings in some different strands. What about B cells?

 

[Mohawk1995]

Their findings don't seem to match with what Stanford is seeing. According to Ron Davies the problem is in the serum, not the cells.

Maybe the "thing" in the serum is causing the receptors dysfunctioning and nothing wrong with them structurally. Griffith team should repeat the tests with ME/CFS cells in healthy serum.

I agree with @melihtas in that this is not at odds with the work at Stanford. I am not sure Davis is saying that the "problem" is in the serum. He is noting that there is a dysfunction occurring in the Serum. There is of yet no explanation for what is creating that. Looking further upstream will be the best bet in determining this.

The fatigue is almost certainly due to changes in cellular metabolism, but on such a widespread basis it must be systemic (which makes sense with the serum issue identified). What is creating the changes in the Serum? Most likely a hormonal or electro-chemical activation of the "organs" in the body that produce the substances in the Serum. What is signalling the activation of these organs? Most likely a Neuro-Immune response. What is causing that? Things start to get gray there.

 

[Valentijn]

I don't understand the negativity in this post. We spend our time begging for biomedical research and then pooing all over the the scientists and thier research when they publish results.

I appreciate the good PR about ME/CFS being proven biomedical, but the science aspect is fairly useless. They have a history of reporting results which haven't been corrected for the risk of false positives when making dozens or hundreds of comparisons. And some other bizarre stuff which portrayed results in a very misleading manner.

That said, they've been forced to work with small samples of patients, probably due to limited funding. That's the other reason I'm glad to see them making waves - that's how researchers get funding, as we've seen from the BPS school in the UK. And with more funding, they should be able to conduct larger and better studies with reliable results.

But unless they have a new study out, with proper methodology, there's absolutely no reason to hope that they've made an actual breakthrough at this point in time. They haven't. But hopefully they'll keep trying, because they're looking in the directions which we need researchers to look.

I've been saying for a while that there seems to be a problem with glucose metabolism due to patient reports of reactive hypoglycemia, hypoglycemia like episodes but without actual low blood sugar, poor fasting tollerance, the beneficial effect of small frequent meals.

I've been having ongoing false hypos at 4.8 and lower during the day, since developing diabetes. I'm actually trying to keep my blood sugar over 5.0 currently to avoid it. But I'm not sure if it's due to some ME thing, or due to consistently having blood sugar at 10.0-11.0 most nights and my body not being able to get a chance to get used to normal levels.

 

[carer51]

Thank you, phoenix rising, for being a place I can come and check the facts when something like this pops up!
At least this looks like something that a GP might actually take relatively seriously if anyone tries to suggest James' illness is psychosomatic again, although it does seem less significant than some of the other research we're seeing here, and a little redundant. I too would like to roll it up tightly and carry it around with me for certain special occasions such as that.

 

[mango]

Has been picked up in Sweden too, by a health related website:

https://www.dh.se/kroniskt-trotthetssyndrom-ar-en-sjukdom/

Google translate, English:
https://translate.google.se/transla...kt-trotthetssyndrom-ar-en-sjukdom/&edit-text=

 

[wastwater]

Think I saw trpm3 has something to do with the retina and pax6 a location for riegers syndrome

 

[boolybooly]

Question is, is this poor calcium (edit) channel expression response in CFS NK cells replicable? 15 patients is a tiny sample. That kind of study can blow away in a light breeze. NK cell studies in CFS have been notoriously difficult to replicate and get a consistent result.

Take away for me is Griffiths studies need replicating before we can consider them useful. We don't want another XMRV.

 

[alicec]

Their findings don't seem to match with what Stanford is seeing. According to Ron Davies the problem is in the serum, not the cells.

It's entirely possible that the results are compatible.

The authors use two justifications for assuming there is some fundamental difference in NK cells from CFS/ME patients - the supposed differences in TRPM3 SNPs (which they know don't actually exist) and their previous studies showing reduced NK cell activity in patient's cells.

Well the first doesn't really exist and the second is a result that is often not replicated. Some labs have found reduced NK activity, many have not.

So actually there is no particular reason to think that these results are inherent in the cells, much as the authors would like us to believe this.

It is quite possible that the cell differences are the result of their previous existence bathed in serum. They have now been removed from the serum but it may take time for the effect of the agent(s) in CFS/ME serum on the cells to subside.

This is also a potential source of uncontrolled variability in assays of isolated cells. Small differences in processing time (that unexpected phone call, a machine that is not available etc, etc) could have a big effect on the cellular activity.

Maybe this too is the source of the inconsistent NK cell activity studies. There could be significant though small and unrecognised differences in processing of different laboratories which make a big difference to the outcome.

In other studies on energy production by PBMC from CFS/ME patients compared with controls, we have already seen discrepancies which may well be due to differences in processing of cells (ie cells isolated and tested fairly quickly vs cells cultured for several days before testing). This is discussed here and here and at various points in these two threads.

 

[alicec]

class of receptors TRPM3 belongs to are also known as 'threat rececptors', because they're upregulated when the body is under any kind of threat, such as infection, trauma, or even childbirth.

The authors draw this to our attention but interestingly they found that the receptors are decreased on the minor NK cell component, normal on the major component.

 

[kangaSue]

3) faulty TRPM3 receptors perceive serious ongoing threat (even if virus etc eradicated)

TRPM3 channels are activated by sphingolipids. There's a current big thread that draws sphingolipids into the mix;
http://forums.phoenixrising.me/inde...ephalopathy-cfs.48446/page-35#post-815433RPM3

 

[adreno]

It's entirely possible that the results are compatible.

Yes, but the authors' claim that ME/CFS is due to a defective cell receptor is not.

 

[JamBob]

I've been having ongoing false hypos at 4.8 and lower during the day, since developing diabetes. I'm actually trying to keep my blood sugar over 5.0 currently to avoid it. But I'm not sure if it's due to some ME thing, or due to consistently having blood sugar at 10.0-11.0 most nights and my body not being able to get a chance to get used to normal levels.

False hypos (I call them "relative" hypos) are a known thing in diabetes. I get them when I have been running high blood sugars for some time and then start to lower them. You can also get them if you drop your blood sugars really quickly.

I am convinced that when people with ME are saying they have hypos (but they have normal blood sugars) that it is actually symptoms of dysautonomia that they are experiencing. I have dysautonomia and IDDM and the autonomic symptoms you get with hypos are identical to dysautonomic symptoms. It's only by testing my blood sugar that I can tell the difference.

 

[A.B.]

I am convinced that when people with ME are saying they have hypos (but they have normal blood sugars) that it is actually symptoms of dysautonomia that they are experiencing. I have dysautonomia and IDDM and the autonomic symptoms you get with hypos are identical to dysautonomic symptoms. It's only by testing my blood sugar that I can tell the difference.

I'm not convinced the "false" hypoglycemia has nothing to do with blood sugar (or more specifically, cellular energy status). I think the body is just successfully avoiding hypoglycemia, or that the problem is not the level of glucose in the blood but perhaps an energy deficit in the cell. Remember that we seem to have an inability to efficiently turn glucose into ATP. Many of the symptoms of hypoglycemia are caused by glucose counterregulation (more specifically, by release of adrenaline), not by blood sugar itself. If the counterregulation succeeds (and there is no reason it wouldn't) then blood glucose might very well be fine by the time it is measured. The body is probably better at knowing when there is an energy deficit than a glucose meter with a drop of peripheral blood. It also doesn't seem far fetched to speculate that the response to rapidly dropping ATP levels in the cell might be very similar to that of hypoglycemia.

The definition of hypoglycemia, and relevant guidelines are probably built for diabetics and assume that in the cell there are no problems actually making ATP from fuel. I'm speculating here but the point is that we may be dealing with a previously unrecognized problem where the current assumptions are wrong.

Personally I frequently have a feeling similar to what comes before the hypoglycemia, while actually rarely going into actual measured hypoglycemia. This improves somewhat with eating. I don't think it would if it were a form of dysautonomia.

 

[alex3619]

Remember that we seem to have an inability to efficiently turn glucose into ATP. Many of the symptoms of hypoglycemia are caused by glucose counterregulation (more specifically, by release of adrenaline), not by blood sugar itself.

I meet the technical definition for a diabetic but I am highly atypical. I have long suspected this is more like a less common side effect from ME. I have however seen low blood sugar, low enough I should be unconscious ... yet aside from hypoglycemia symptoms, including shaking, I am otherwise fine, though I do eat carbs when this happens. We are adapted to a low energy state in my current opinion.

 

[Molly98]

I'm not convinced the "false" hypoglycemia has nothing to do with blood sugar (or more specifically, cellular energy status). I think the body is just successfully avoiding hypoglycemia, or that the problem is not the level of glucose in the blood but perhaps an energy deficit in the cell. Remember that we seem to have an inability to efficiently turn glucose into ATP. Many of the symptoms of hypoglycemia are caused by glucose counterregulation (more specifically, by release of adrenaline), not by blood sugar itself. If the counterregulation succeeds (and there is no reason it wouldn't) then blood glucose might very well be fine by the time it is measured. The body is probably better at knowing when there is an energy deficit than a glucose meter with a drop of peripheral blood. It also doesn't seem far fetched to speculate that the response to rapidly dropping ATP levels in the cell might be very similar to that of hypoglycemia.

The definition of hypoglycemia, and relevant guidelines are probably built for diabetics and assume that in the cell there are no problems actually making ATP from fuel. I'm speculating here but the point is that we may be dealing with a previously unrecognized problem where the current assumptions are wrong.

Personally I frequently have a feeling similar to what comes before the hypoglycemia, while actually rarely going into actual measured hypoglycemia. This improves somewhat with eating. I don't think it would if it were a form of dysautonomia.

I agree. In my case I also have POTs and for years have suffered what seem like quite severe hypoglycemic episodes, which I feel are not POTs related but energy and blood sugar related and what I feel make a lot more sense given the latest research on our inability to metabolize sugars.
These particular symptoms are complete relieved by having a meal and get worse the longer I go without food.

Last year I got quite into following professional cycling and listened to a couple of autobiographies by top cyclists Chris Froome and G Thomas. What really struck me is that in the world of cycling they use this term 'bonking' which is an expression used where a long distant cyclist literally hits a wall where their glucose level is so depleted that they suddenly have no energy and it affects their eye sight, their cognition, balance, muscles everything very suddenly.

What they describe is exactly what happens to me only I have not cycled 100 miles up hill. The trick for a cyclist is to replenish glucose levels consistently so that they never reach the stage where their bodies 'bonk'.

My guess is that if we are unable to metabolise glucose we are literally 'bonking' all over the place with the minimal of Exertion. Google it, you will probably find what they describe very familiar.

https://tunedintocycling.com/2008/05/10/cycling-nutrition-the-bonk/