Sphingolipids as a treatment avenue?

[AdamS]

From Naviaux's paper here

The dominant finding from the pathway analysis was that sphingolipid abnormalities constituted close to 50% of all of the metabolic disturbances associated with CFS in both males and females.

I know it's a few months old now but this is a pretty big finding right? Questions...

• Are there any other illnesses which have similarly low levels of Sphingolipids?
• Is there a way to replace lost Sphingolipids/ceramides and would doing so have a positive impact for ME/CFS patients?
• How do low sphingolipids relate to sugar metabolism? Are they a consequence or cause of PDH being blocked?

Thanks, Adam

 

[A.B.]

Serum sphingomyelins and ceramides are early predictors of memory impairment
(in Alzheimer's disease)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783210/

individuals with the highest levels of blood ceramides were found to have a threefold to fourfold greater risk of suffering a cardiovascular event compared with those with the lowest ceramide score

https://www.acc.org/about-acc/press...od-help-predict-cardiovascular-events?w_nav=S

Having low sphingolipids and ceramides could be a good thing. It could also be bad. We need more research to figure out what is going on.

PS: one way this could make sense is that ceramides act as signals telling cells to die, and with our bodies in a Dauer-like state a priority would be to slow down cell death.

Programmed cell death induced by ceramid
https://www.ncbi.nlm.nih.gov/pubmed/8456305

 

[lansbergen]

Programmed cell death induced by ceramid

Maybe thats one of the reasons levamisole helps me.

Levamisole induced apoptosis in cultured vascular endothelial cells

 

[Jesse2233]

@AdamS have you read @JaimeS's article on sphingolipids? It's fascinating and prompted a call from Dr Naviaux himself

Should probably have it's own thread on here somehwere

 

[Alvin2]

Vitamin K2 MK4 is required for sphingolipid synthesis, but it has no effect on this condition, i've tried it at quite high doses.

 

[AdamS]

@AdamS have you read @JaimeS's article on sphingolipids? It's fascinating and prompted a call from Dr Naviaux himself

Should probably have it's own thread on here somehwere

I sure have, it's brilliant!

 

[prioris]

I don't see this leading to anything big but maybe some supplement will get created to help with mitigating a few symptoms.

Whenever I see ME/CFIDS research focusing on mitochondrial stuff, I become suspicious that the researcher thinks the disease is about some energy or fatigue problem. Many get brainwashed so don't really understand the disease. These researchers need to be reminded there is brain inflammation. Also remember that most probably got secondary fibromyalgia too. It's really a kind of systemic disease with potentially a gazillion symptoms.

Hypometabolism means an abnormally slow metabolism. In other words, the body as a whole is not producing enough energy. As energy is made inside cells, this is where hypometabolism originates. Cells do not produce enough energy because their mitochondria are not working properly (mitochondrial dysfunction).

 

[JaimeS]

These researchers need to be reminded there is brain inflammation.

Would that there were better research saying so.

Hypometabolism means an abnormally slow metabolism. In other words, the body as a whole is not producing enough energy. As energy is made inside cells, this is where hypometabolism originates. Cells do not produce enough energy because their mitochondria are not working properly (mitochondrial dysfunction).

The molecules with energy-rich bonds do not have to be made in the mitochondria. Some are made during glycolysis, which does not occur within the mitochondria.

 

[prioris]

>Would that there were better research saying so. [brain inflammation]

that's already been proven (but not to the powers that be covering up the disease
but who cares what they think)

 

[nandixon]

How do low sphingolipids relate to sugar metabolism? Are they a consequence or cause of PDH being blocked?

It's theoretically possible for either to be the case:

[As a consequence]
The de novo (i.e., from scratch) synthesis of sphingolipids requires acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is made from pyruvate by the pyruvate dehydrogenase (PDH) complex. If the PDH complex is inhibited, as Fluge & Mella’s work suggests, then the supply of acetyl-CoA may be low and hence sphingolipids may be low.

[As a cause]
If sphingolipids are low for some other reason, then the supply of the signaling molecule sphingosine-1-phosphate (S1P), which is made from sphingolipids, may be low. S1P has numerous targets including the PI3K/Akt/mTORC1 pathway. If that pathway is not being sufficiently activated it may lead to inhibition of the PDH complex.

So there is potentially a cyclical “chicken and the egg” relationship between sphingolipids and the PDH complex.

 

[Emily L]

I'm sorry but I don't understand any of this

Can someone please explain what these words mean?

 

[JaimeS]

@Emily L maybe take a look at the article tagged earlier? I can't promise it will be super-illuminating, but it's a start.