Lactic acid, lactate in ME/CFS

[forestglip]

But anterior cingulate isn't all round the ventricles - i.e. it doesn't really add up.

Well, I was thinking cells throughout the brain could have high lactate. Not localized necessarily. Maybe all neurons or all of a certain glial cell.

 

[Jonathan Edwards]

Well, I was thinking cells throughout the brain could have high lactate.

I presume someone would have reported it if so.

 

[Nightsong]

Just to add that in the most recent one of these studies, the poster presentation (link), the task was a visual stimulus, as opposed to some of the other studies that have assessed lactate at baseline or post-exercise:



It would be useful, I think, to have a lactate MRS study with an additional physically inactive comparator group, and to examine the effects of both light physical & cognitive exertion.

 

[ScoutB]

One study tested lactate using both methods, but it was only high when using MRS, as mentioned below.

Ah interesting, that is really handy to have.

it is conceivable that lactate reflects not metaboolic changes but CSF flux/stasis changes. The CSF is made in the ventricles and ends up in the spinal tap. Ventricular CSF might have more lactate if brain uses it up as a substrate, or less, if brain produces it and it leaks out at the perimeter.

Am I understanding you correctly: the suggestion is maybe the brain is both making more lactate and also using all that lactate before the CSF reaches the spinal tap?

I had forgotten that in the brain we now think of lactate as being a fuel source rather than a waste product.

Actually, looking into that, this quote from wiki might be answering our question:

Although glucose is usually assumed to be the main energy source for living tissues, there is evidence that lactate, in preference to glucose, is preferentially metabolized by neurons in the brains of several mammalian species that include mice, rats, and humans. According to the lactate-shuttle hypothesis, glial cells are responsible for transforming glucose into lactate, and for providing lactate to the neurons. Because of this local metabolic activity of glial cells, the extracellular fluid immediately surrounding neurons strongly differs in composition from the blood or cerebrospinal fluid, being much richer with lactate, as was found in microdialysis studies.

(I guess we still need to figure out if that would explain the ventricles having more lactate too.)

I also found this study: Lactate supply overtakes glucose when neural computational and cognitive loads scale up. From skimming, it sounds like they gave rats cognitive tests (an easier one and a harder one) and found that if they injected the rats with oxamate (which, I gather, blocks lactate production), the rats could still do the easy task but did more poorly on the harder task. They argue this shows that while the brain uses both glucose and lactate as a fuel source, lactate is needed for more advanced/energy-intensive cognitive tasks.

So if the findings of these studies pan out -- sounds like ME/CFS neurons might be requiring (or at least receiving) more lactate than healthy controls need for equivalent cognitive tasks? (as in that poster Nightsong just posted). Seems pretty compelling to me.

 

[Jonathan Edwards]

So lactate might be a good thing, produced to help neurons do hard cognitive tasks?

It all seems rather complicated and I have a nasty suspicion that people doing studies on lactate, wherever, in ME/CFS work on the simplistic assumption:

lactate = bad = metabolic failure = ME/CFS = bingo.

 

[Turtle]

Could the brain prefer lactate as fuel, when oxygen is low?

 

[ScoutB]

It all seems rather complicated and I have a nasty suspicion that people doing studies on lactate, wherever, in ME/CFS work on the simplistic assumption:

lactate = bad = metabolic failure = ME/CFS = bingo.

Yes, and if it holds up that lactate is disappearing (i.e. being used up?), leaving levels normal in CSF, then maybe that's a point in favour of it being something the neurons are successfully using, rather than the side effect of a lack of oxygen?

I wonder if there's some other metabolite we would expect to be raised in the cerebrospinal fluid if the lactate is indeed being used as an energy source.

Could the brain prefer lactate as fuel, when oxygen is low?

Yea I'm curious too why the brain would prefer lactate. Biology folks correct me if I'm wrong, but I believe the deal with lactate is that it is a useful fuel when you have oxygen, and a 'waste product' when you don't? (Probably waste product is unfair, but what I mean is: the no-oxygen ways of getting energy *produce* lactate rather than use it, I think?)