VLCFA as a disease biomarker: If elevated VLCFAs... - AMN EASIER


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VLCFA as a disease biomarker

bluejadedwho profile image

If elevated VLCFAs Is a biomarker of the disease, then why does lowering them not affect disease progression?

11 Replies

Because it does not cross the blood brain barrier

It all depends which scientific report you read. So little research has been done on our disease.


The exact mechanism that links the VLCFA excess to axonal degeneration in AMN or to inflammation and demyelination in cALD remains elusive.

VLCFA's do indeed cross the blood brain barrier according to this:


Since the reduction of accumulated VLCFA in the brain is thought to be crucial for preventing the progression of neurologic symptoms in X-ALD, compounds that can cross the blood-brain barrier and decrease the VLCFA levels in the brain would be a highly attractive candidate for effective treatment of ALD patients.

And, indeed, this:


It is thought that high levels of VLCFAs in the brain are associated with the increased production of cytokines, immune proteins that trigger inflammation. Inflammation is an immune process that can lead to damage and swelling. This results in the progressive loss of the myelin sheath, or demyelination. The myelin sheath is the insulating layer that protects nerve fibers from damage and ensures that nerve signals are sent from the brain to muscles without being lost.

Furthermore, increased VLCFAs levels may destabilize mitochrondial membranes in brain cells. Mitochondria, sometimes referred to as the powerhouse of the cells, are essential for energy production. The mitochondrial membrane normally tightly regulates what can go in and out of the mitochondria, and by disrupting this, VLCFAs may impair the energy production process and increase the production of other damaging substances inside cells. This can result in the death of brain cells.

Similarly, in the adrenal glands, the accumulation of VLCFAs may cause mitochondrial dysfunction and lead to progressive cell death. It may also be possible that a hormonal imbalance is caused by excess VLCFAs being added to the membrane of the adrenal glands and preventing it from receiving signals from the rest of the body.

The question is, how are you going to lower the VLCFA's?

My neurologist has been prescribing me Valproic Acid for the last couple of years to try and lower them.


A 6-month pilot trial of VPA in X-ALD patients resulted in reversion of the oxidative damage of proteins in peripheral blood mononuclear cells. Thus, we propose VPA as a promising novel therapeutic approach that warrants further clinical investigation in X-ALD.

There are other candidate drugs out there I have posted about.

There is also the possibility of upregulating ABCD2.

Metformin, of which MIN-102 is a derivative has been shown to upregulate ABCD2 and lower VLCFA levels.


Metformin lowered VLCFA levels, improved mitochondrial function and ameliorated inflammatory gene expression in X-ALD patient-derived cells.

It is a complicated disease, haven't touched on the hormonal issues yet. But I am prepared to accept that the buildup of VLCFA's leads to inflammation, which leads to demyelination and a destabilisation of mitochondria.

Kranal profile image
Kranal in reply to monkeybus

I read scientific reports too, but - as a parent - I find it difficult to get the salient facts out of them. Thank you so much for sharing your knowledge with us.

If there ever was an example of “long story short” these two responses get it done. Great information, most I’ve never read before. Then a one line response. Effective and efficient all in two responses.

A while ago, I heard that our bodies also produce VLCFA. An interesting read: ncbi.nlm.nih.gov/pmc/articl...

Also, Min-102 has been shown to reduce brain lesions which is why I'm back on it. Yeah, science! However, my last MRI which I 'm awaiting the Lowes score, may show some progression. I'm going back to the high antioxidant cocktail along with Min-102 and see what happens. As I tell the docs, this is very interesting. I've learned so much. My curiosity is piqued.

my guess is that this is something to do with blood plasma levels of VLCFA not being particularly sensitive to in-cell levels of VLCFA which is where the damage takes place

Watch the movie Lorenzo's Oil. They eliminated his intake of VLCFAs and his body generated them to compensate. That's why Lorenzo's Oil is used for treatment. It fakes the body out.

monkeybus profile image
monkeybus in reply to twbuckner

I should think we've all seen/ heard of Lorenzo's Oil.

Trouble is, it doesn't work for symptomatic adults.

From Nature Magazine:


But the timing of treatment is crucial. “Give the oil as soon as you know your son carries the genetic defect. If you wait, the symptoms might come and then you are in a different ballpark”, Lorenzo's father, Augusto Odone, told the New Scientist (UK, 26 September).

From the British Medical Journal:


New England Journal of Medicine:


No good news for us AMN folks here

If there was even the merest hint that it actually worked, I'd be glugging it by the gallon.

I wish I'd started on it when I was a kid, way before any symptoms manifested.

This has been a question of mine for a while. In females, vlcfa can be in the normal range and a diagnosis missed even with significant symptoms and signs. Others have very high levels and are asymptomatic. So the correlation of serum VLCFA level to signs/symptoms/disability just doesn’t work out. As a bio marker, it certainly is helpful in diagnosis but the high VLCFA levels may not be the actual cause of the damage or at least not all of it. Other things must be going on “behind the scenes” and new pathophysiological bio markers are needed to actually follow the progression or remittance with treatments.

monkeybus profile image
monkeybus in reply to tieaknot

tieaknot, you make an excellent observation (as always).

Of course, women aren't men. And that ain't just skin deep. It's to the core. Most drugs are tested on male volunteers, and they affect women differently to men. Often to the detriment of women.

Sex Differences in Pharmacokinetics and Pharmacodynamics


I am flying off on a tangent here, but back to VLCFA levels. Of course mine are "high" but I don't know the number. I don't know what the normal range is. I was told by my neurologist ages ago. But, I had a lot of info to take in at the time, I just didn't care.

Really (and this will never happen), we should all post our numbers, ages and symptoms here and see if there any correlations.

It'll be like how we never posted our ABCD1 mutations.

I am seeing my neurologist later this month. I'll ask him mine.

tieaknot profile image
tieaknot in reply to monkeybus

I agree monkeybus!

Just figure in terms of pathogenicity, females could be a good way to observe it since the actual levels of VLCFAs do not seem to correspond to the level of disability or progression. It may help us to untangle what is only a pathoneumonuc bio MARKER for ALD and what is the actual pathophysiology behind the disease/damage/symptoms/signs and progression. 😉

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