Fixing low cerebral vitamin B5 pantothenic acid as an approach to possibly reversing neurodegeneration & dementia in Alzheimers Huntingtons Parkinsons [myelin commonality]
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@DavidPS Same here, especially that I got symptoms of Parkinson's that was self-induced be my carelessness. Have my stash of B5, but didn't know how to get started on the right footing. This helps. Thanks @cs3000 and @CrumblingCookie
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The crucial SMVT also becomes severely downregulated by alcohol and its metabolites acetaldehyde and ethylated fatty acids. This is a profound impact; it's part of what's behind the neurological impairments caused by chronic alcoholism. I don't think B5 receives the necessary credit in that disease either because for some odd reason they put their focus on biotin depletion. The nervous system however holds on very dearly to their biotin stores in comparison to other tissues so I assume brain B5 stores will have been abyssmally low long before. brain biotin stores become significantly depleted.
Another influence:
Endotoxins / LPS also severely downregulate the SMVT through a TLR-4-dependent signal cascade.
What's the biological logic behind that? Maybe it's sensible for the cells to be told to hold still about their PA needs and proliferation whilst there is nearby infection, to allow for more PA to be taken up by the required immune cells (which hugely depend on increased PA influx proportionately to their proliferation and immune activity) so that they can clear things up first.I can't say which studies I've taken that from but they were easily accessible.
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It appears that high amounts B5 supplementation may cause sleep issues after a few months. In Dr. Stasha Gominak's clinical practice she found that her patient's sleep improved using the combination of vitamin D and various B vitamins. She noticed sleep issues returned and that her patients needed to lower their supplementation to restore sleep.
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@DavidPS
Gominak is predominantly "thinking out loud" in her writings. It's all hypotheses, incomplete observations and in a context of an IMO very false underlying premise of what the Ds actually do.
Dropping her latter false assumption she's essentially saying:
"The change in the make-up of the intestinal bacterial population ... has resulted in an accompanying pandemic of B5 deficiency." Which I think may be very true.
Her observations of immediately worsened sleep and feelings of slight agitation in her 50 test patients on 400mg PA per day are reasonable.
Her decision to have immediately dropped the PA within 1-2 days and build her deductions and strange contradictions on this immediate effect, however, was not.
And here's why: B5 will have such an immediate effect even (or perhaps especially so?) in deficiency. Not least because of its essential influence on reinstating ACTH-responding adrenal hormone release.
IME this lasts for a few days to a week upon starting B5 supplementation as a transient adaptation effect.Her observations of overdoing B100 causing issues are likely to stem from biotin (which drastically worsens PA availability) or the excessive pyridoxine (crap B6) and excess folate (which was probably even folic acid).
Wrt to too much biotin and impaired B5 this could be a typical example of how B complex products actually severely screw things up. -
@CrumblingCookie great insight, its also sodium dependant transporter so you can throw excessive salt restriction recommended to the elderly on top of that
(btw B5 can increase immune activity in the gut. it raises il-22 which recruits neutrophils there. 500mg is an experiment for food poisoning or when a stomach bug is going around, preventatively or just at early signs. B5 can worsen auto-immune infiltration issues in the intestine though, by experience it didn't hit as noticeable at 100mg as 500mg - 1g)
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@cs3000 said:
500mg is an experiment for food poisoning or when a stomach bug is going around, preventatively or just at early signs. B5 can worsen auto-immune infiltration issues in the intestine though, by experience it didn't hit as noticeable at 100mg as 500mg - 1g)
That's a good and practical hint which I'm going to note down!
It becomes tricky with the delicate immune homeostasis of the GI mucosa as soon as infections have firmly established themselves...Taking your experience a step further:
Should an overly strong sensitivity to quality and allergenic composition of foods then urgently raise suspicions of a CoA/B5 deficiency?
In animal experiments, B5 deficiency reliably induces Irritibale-Bowel-Syndrome disease.
Which is curiously even ameliorated by antibiotic treatment which suggests an interaction with the microbiome in the pathomechanism. I.e. taking antibiotics in such a case is merely suppressing symptoms but not tackling the underlying cause.I'm also not getting why the common "Peatist" hasn't awarded this any due attention yet, given so many cascara-eating and endotoxin-fearing, constipated folks.
Pantothenyl alcohol = dexpanthenol = pantothenol e.g fixes atonic = adynamic ileus, dose-dependently. They compared control with 125mg once or up to 750mg twice daily:A pilot study of the effect of pantothenic acid in the treatment of post-operative ileus: results from an orthopedic surgical department
For a reference and relativization of the adequate dosing schemes in comparison to the puny 5mg "daily adequate intake":
I've looked up the leaflet of the Italian-made Bepanthene 250mg/mL and therein it's recommended to take 1-2 ampoules 2-3 times weekly for 6 weeks.
I.e. 500-1000mg every other day of intramuscular, fully absorbed B5.
That's 6,000-18,000mg over the course of six weeks to assumedly reach re-sufficiency of peripheral tissue CoA in the treatment of the rather "minor", "trivial" ailment of diffuse alopecia.
When looking for studies it's necessary to use the terms pantothenic acid but also pantothenyl alcohol, dexpanthenol, pantothenol.
There were many studies done in the 50s and 60s (pantothenyl alcohol).
One of them makes the IMO generally very important summarization:"Following stress there may be an increased utilization of pantothenic acid in the production of acetylcholine".
That opens up so many implications. Not least the hypotheses and observations of consecutive brain energy depletion mechanisms by any kind of severe stress, be it physical or emotional trauma, like those depicted by Dr. David Stephens in his glucose trials.
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what would be a safe way to increase B5
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"Although the etiology of Alzheimer's disease includes a wide range of dysfunction, the most essential dysfunction is probably in the mesolimbic acetylcholine (ACh) system.*"
I've also noticed a couple of things.
- On the former RPF haidut had once posted about significant benefits of a high biotin (>100mg pd) trial in brain diseases. But in follow-up trials it turned out that those results couldn't be replicated at all or only very slightly. And that lower but still excessively high doses of 10mg or so were completely useless.
So if it's about the SMVT there are of course two implications:-
- Less than optimal CNS biotin will be a mere tip of the iceberg.
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- High dose biotin will be both mostly inadequate and able to make things worse.
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- R(+) alpha lipoic acid (R-ALA) is known of course for being a powerful antagonist of nitrative/nitrosative radicals whilst also being actually mildly oxidative.
There's lots of research and succesful use of ALA against all kinds of neurological diseases including Alzheimer.
ALA is also transported by the SMVT.
There's discussion about whether such extracellularly-imported ALA reaches the mitochondria or if it only acts in the cellular cytoplasma.
The crucial PDH complex is also present in the cytoplasma, where it yields acetyl-groups from pyruvate to supply the requirements of e.g. acetylcholine.
Presumably, much of the positive effects of ALA in neurodegeneration (nitrative stress, oxidative stimulation of Akt and enhanced GLUT4 aside) stem from providing the much needed acetyl-groups for acetylcholine.
Edit:
It looks as if ALA uptake happens only partly through the SMVT, but predominantly through a proton-linked monocarboxylic acid transporter (MCT) 1,2. Which admittedly relativizes the either the importance or the necessary quantity of R-ALA in this context. - The piracetam group of drugs, used against neurodegeneration in general and Alzheimer and also as a popular nootropic, is being assumed to predominantly act through enhancing muscarinic ACh receptors density. I.e. postsynaptic ACh action. It also speeds up the whole ACh metabolism (synthesis and breakdown).
In order to maintain its benefits and to not crash it's thus been reported (not in the packaging leaflets, of course) that piracetam really requires a generous dietary choline intake. But that's half-arsed advice and again not the end of it because there'll be just as much depletion of B5.
Overall, I'm seeing much and many different approaches against neurodegenaration all circulating and pointing towards impairments of SMVT activity.
I need to think of B5 in a steady combination with R-ALA and choline. And crank up the biotin only as part of such a combination and likely only secondarily. Only then should I consider megadosing pure dextrose or iodide or other things.With Acetyl-CoA and the ACP acyl-carrier-protein being dependent upon B5 and PDH that will also impact my approach to HDAC inhibition as we naturally need to raise acetylation levels for concurrent inhibition of deacetylation to have any meaningful effect on the balance of histone acetylation after all.
@visalibero I'm currently i.m. injecting 500mg dexpanthenol eod. I feel like oral or i.m. Dex is "smoother" in its action than oral pantothenic acid – maybe by higher tissue distribution – but also insufficient. So I'm in high anticipation of trying pantethine (600-900mg pd per os). That form should be best.
- On the former RPF haidut had once posted about significant benefits of a high biotin (>100mg pd) trial in brain diseases. But in follow-up trials it turned out that those results couldn't be replicated at all or only very slightly. And that lower but still excessively high doses of 10mg or so were completely useless.
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I've noticed that with eod 500mg dexpanthenol i.m., the previously noticed effect of significantly smoother skin (e.g. on the back of my hands) disappeared.
I need at least 1,000-1,500mg dexpanthenol per day (p.o.) for this effect to acutely come back (within a day) and to maintain.
It would be interesting to know the equivalent dose of pantothenic acid to reach this individual effect threshold but I don't have any PA left to find out. All I know is that 4-8grams of PA per day is not uncommong among bodybuilders to contain their skin breakouts. And similar quantities of PA are necessary in some few non-steroid-abusing people.
Maybe someone on this forum who's doing PA could compare his/her necessary dosage with Dex?
It makes one wonder why those PA levels can become so low!
Still wondering whether it's all down to (aquired, medically induced) insufficiency of SMVT function,
or whether there's strongly increased expenditure of B5 and CoA in today's people which surpass the once physiological uptake capacities.
I was thinking: Wouldn't it be morbidly funny if even aluminum was involved and a known inhibitor of SMVT? But I couldn't find anything further on SMVT inhibition.What I did find was the novel discovery (only in 2017) of CoA-lation, which is posttranlational modification of important proteins:
Coenzyme A first shows up as CoA-SH and can form dimers of itself to CoA-S–S-CoA.
Just as that, it can also associate with the cysteine in over 500 cellular and predominantly metabolic enzymes. This happens in response to increased cellular, oxidative stress.
By this way the CoAlated proteins are reversibly protected from irreversible oxidation.
It depends on protein structure whether it requires CoAlation or glutathionylation.
In essence, CoAlation is about as important to protect cellular proteins as glutathione,
and they cannot replace each other's functions.Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells
Protein CoAlation and antioxidant function of coenzyme A in prokaryotic cells
There's also a finding that the increased levels of malonic acid encountered in vitamin-B12-deficiency strongly stimulates CoA synthesis. I.e. the sequestration of CoA to malonyl-CoA (or propionyl-CoA) strongly stimulates more CoA synthesis.
Effectively, there are significantly increased intracellular CoA reserves in B12-deficiency because of that.
What this means practically is not yet quite figured out.
As soon as someone corrects a rather common and widespread B12-deficiency those increased CoA reserves will decrease.
I suspect what this means is that when supplementing B12 one (unknowingly) becomes committed to also tackle this topic of B5 uptake, SMVT, CoA availability. Not doing so could open up another and steeper pit.
