Different Nor(epinephrine) responses to exercise and insulin stressors in CFS patients

[Simon]

A novel and very interesting finding that CFS patients have a normal adrenaline response to insulin stress but an abnormal one to exercise. Small study, but intriguing, especially given the link between faulty adrenaline production and fatigue.

Making sense of the terminology: adrenaline, norepinepherine, catecholamines etc

This is basically about the 'Fight or Flight' response. Epinepherine is another name for adrenaline, the "Go!" hormone produced by the adrenal glands to kick start the body into action.

Norepinepherine is the same as noradrenaline and is a cousin of adrenaline that is also involved in the flight or flight response, both as a neurotransmitter (signal between nerve cells) and as a hormone (diffusing more widely in the body).

Both adrenaline and noradrenaline are a category of molecule known as catecholamines

Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome - Jana Stahler 2013

Highlights

• CFS patients showed diminished catecholaminergic responses to an exercise stressor.
• They showed unaltered catecholaminergic responses to a pharmacological stressor.
• Exercise seems to be an important stressor for CFS patients.
• Inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.


Abstract

Chronic fatigue syndrome (CFS) is characterized by fatigue lasting 6 months or longer. CFS has been associated with a disturbed (re-)activity of the autonomic nervous system. However, the sympathetic adrenomedulla (SAM) remains under-examined in CFS.

To investigate SAM reactivity, we implemented a submaximal cycle ergometry (ERGO) and a pharmacological test (Insulin Tolerance Test, ITT) in 21 CFS patients and 20 age-, sex-, and BMI-matched controls. Plasma norepinephrine and epinephrine were collected once before and twice after the tests (+10/+20, and +30 min).

Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls, while the groups did not differ in their responses to the ITT.

To conclude, we found evidence of altered sympathetic-neural and SAM reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients. It is conceivable that inadequate catecholaminergic responses to physical exertion might contribute to CFS
symptoms.

Trying to access the full text

 

[Shell]

That looks interesting. I wonder how they dx the CFS. I wonder because the abstract looks like hyperadrenergic POTS (not that they have increased HR in the abstract) Or could these patients have a hyperad thing without POTS?
Questions questions...

 

[Gijs]

ME is a stress respons disorder just like dr. Kogelnik said. I agree. The cause what triggers this abnormal reaction will be the key to explain this disease. The immune problems are secondary but important to tread.

 

[MeSci]

I was surprised by "Lower baseline levels and attenuated responses of epinephrine to the ERGO." As I and many others often feel 'tired but wired', which many of us attribute to adrenaline surges, could it be that we produce high levels at times other than during physical activity? I used to get major 'adrenaline rushes' shortly after lying down in bed, when I had been relaxed and sleepy - a crazy time to get them! I also used to get particularly 'wired' when I had bouts of nausea combined with urgent hunger. I say 'used to' both times as my low-carb gluten-free diet with supplements has made both phenomena relatively rare.

 

[Simon]

Not for the first time, interesting findings look a lot less impressive close up

The problem with this study is that not only is the sample small (n=21) but there was also a marked difference in response between men and women. So the results for each sex was based on n=10 and n=11 respectively.

Also, one previous study (thanks, Dolphin) found a DECREASE [edited] in catecholamines - as this study did - but that other study used only female patients. Yet there was no DECREASE in catecholamines in females in this study.

So although the idea of an exercise challenge to detect differences in stress response is intriguing, bigger and better studies are needed to find out if there is anything real going on. Sound familiar?

 

[Firestormm]

Sound familiar?

Unfortunately yes, my friend. But thanks for the analysis. I do find this area of research particularly intriguing.

 

[MeSci]

Also, one previous study (thanks, Dolphin) found an increase in catecholamines - as this study did - but that other study used only female patients. There was no increase in catecholamines in females in this study.

I thought the study at the start of this thread showed no increase in catecholamines.

"Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls."

Am I confused?

 

[Simon]

I thought the study at the start of this thread showed no increase in catecholamines.

"Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls."

Am I confused?

No, I am Lower epinepherine levels found in the other study and this one. But for females in this study, levels were normal ie different from the lower levels in the other study (which only had female subjects). Will edit above to correct

 

[A.B.]

This seems to agree with the proposal put forth by Dr. Teitelbaum that HPA axis dysfunction, in particular affecting the adrenal glands, plays a significant role in CFS.

Were other adrenal parameters than epinephrine and norepinephrine measured? Decreased cortisol levels would be expected.

 

[Simon]

This seems to agree with the proposal put forth by Dr. Teitelbaum that HPA axis dysfunction, in particular affecting the adrenal glands, plays a significant role in CFS.

Were other adrenal parameters than epinephrine and norepinephrine measured? Decreased cortisol levels would be expected.

No. But check out the 2001 previous study I mentioned above, which mentions lower adrenocorticotropin. doesn't mention cortisol was lower, but I'd be surprised if they hadn't measured it

 

[ukxmrv]

Does this fit in with the earlier finding my Demitrack et al?

"Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated. Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined."

http://www.ncbi.nlm.nih.gov/pubmed/1659582

 

[biophile]

So much for the state of the art Lighting Process model of increased baseline adrenaline.

 

[Valentijn]

So much for the state of the art Lighting Process model of increased baseline adrenaline.

I'm sure they can find a way to work around this. They'll just have to refer to a vaguer medical dysfunction instead and wave their hands a bit while looking confident.

 

[ukxmrv]

And Gupta. Although it would be harder to be more vague there.

 

[biophile]

They may argue that the normal baseline levels are because the system is burnt-out from chronic overuse and cannot do much to increase levels even during times of need. I vaguely recall one of Cort's blogs about some related research with findings which were the opposite of what one would expect if that was true. It also reminds me of the Light's work on mRNA expression after exercise, IIRC it would appear that we could manifest and/or be sensitive to the effects of adrenaline because the adrenergic receptors are or become over-expressed, not because of too much adrenaline. It would not surprising me however if there is some kind of chronic biological stress involved.

 

[Tom Kindlon]

The women might have also shown significantly lower responses with a bigger sample size: