Fixing low cerebral vitamin B5 pantothenic acid as an approach to possibly reversing neurodegeneration & dementia in Alzheimers Huntingtons Parkinsons [myelin commonality]

[cs3000]

Huntingtons disease,

• Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630497/

Alzheimers disease

• Cerebral deficiency of vitamin B5 (d-pantothenic acid; pantothenate) as a potentially-reversible cause of neurodegeneration and dementia in sporadic
  https://www.sciencedirect.com/science/article/pii/S0006291X20309190

*Pantothenic acid exists at higher concentrations in the brain relative to in blood, being about [10 fold to] 50-fold higher

We found that widespread, severe cerebral deficiency of vitamin B5 occurs in AD. This deficiency was worse in those regions known to undergo severe damage, including the hippocampus, entorhinal cortex, and middle temporal gyrus.
In brain, acetyl-CoA is the obligate precursor of the neurotransmitter acetylcholine, and the complex fatty-acyl groups that mediate the essential insulator role of myelin, both processes being defective in AD; moreover, the large cerebral vitamin B5 concentrations co-localize almost entirely to white matter. Vitamin B5 is well tolerated when administered orally to humans and other mammals.
We conclude that cerebral vitamin B5 deficiency may well cause neurodegeneration and dementia in AD, which might be preventable or even reversible in its early stages, by treatment with suitable oral doses of vitamin B5.

Parkinsons disease

• Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson’s Disease Dementia
  https://www.mdpi.com/2218-1989/11/9/569

It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer’s disease (ADD) and Huntington’s disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson’s disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases.

Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD: the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons.
A targeted ultra–high performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD.

b5 plays a key role in age related cognitive decline , as it's used for myelin / white matter.
Myelin = the sheath around nerves that enables electrical signals to travel well. also b5 is needed for acetyl-coa, for cellular ATP / oxidative phosphorylation / mitochondria function

Vitamin B5 (d-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis
https://pubmed.ncbi.nlm.nih.gov/31759626/

We recently found that cerebral pantothenate is markedly lowered, averaging ∼55% of control values in cases of Huntington's disease (HD) including those who are pre-symptomatic, and that regions where pantothenate is lowered correspond to those which are more severely damaged
Remarkably, cerebral pantothenate was almost entirely localized to myelin-containing structures in both experimental groups
These findings are consistent with physiological localization of pantothenate in myelinated white-matter structures, where it could serve to support myelin synthesis. Further investigation of cerebral pantothenate is warranted in neurodegenerative diseases such as HD and Alzheimer's disease, where myelin loss is a known characteristic of pathogenesis.

an intervention study using pantethine (metabolises to pantothenic aicd), in Alzheimers model
https://link.springer.com/article/10.1007/s13311-019-00754-z

We observed that long-term pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated.

Altogether, our data support a beneficial role for long-term pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of pantethine to alleviate AD pathology. (maybe used ~3000mg human dose 3x a week, has to be converted to pantothenic acid in intestine so assuming would be lower dose for pantothenic acid)

ray thought pantothenic acid is generally pretty safe to take, and said can go up to 100mg - 200mg occasionally

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theres a correlation with higher mortality for people that have high blood pressure with high b5 Association between plasma Vitamin B5 levels and all‐cause mortality: A nested case‐control study but its not an intervention study, so the correlation doesnt prove the b5 as a cause. but maybe something worth looking into with high blood pressure to work out whats going on there. Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism Immunostimulatory effects of vitamin B5 improve anticancer immunotherapy its anti-cancer (pro immunity)

cerebral pantothenic acid may be a key fix of alzheimers , huntingtons, parkinsons dementia, and general age related cognitive decline. and boosting intake of B5 taken by itself away from other b vitamins https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.1986.tb00705.x especially biotin, which reduces the amount of b5 that crosses the blood brain barrier into the brain, may be a nice help for cognition in older age

Also interesting is the lower copper found in brains of people with Alzheimers (and schizophrenia), and copper plays a main role in myelin synthesis.

[DavidPS]

Thanks, B-5 is now on my radar screen. It is one of the B vitamins that I have overlooked.

I am interested in maintaining my cognition for as long as possible. I think that the current environment is making it increasely difficult to to do just that.

[CrumblingCookie]

@cs3000
It makes one wonder why those PA levels can become so low!

The Japanese have looked at
Major involvement of Na+-dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells

which shows PGE2 -> chronic inflammation, NSAID -> given against chronic inflammation, but also DHA -> omega-3 fish oil, given for good circulation and brain improvement (this just gets insidious, doesn't it?) all significantly inhibiting the all-crucial SMVT uptake carrier.

• "Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [3H]biotin and [3H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line"

The SMVT is also responsible for biotin, lipoic acid and iodide uptake. All of which therefore competitively inhibit each other in their uptake.
A major culprit is biotin: Not only because, in absolute amounts, the needs for PA are considerably higher (at least by 100x in comparison to biotin).
But also because intracellular biotin availability signals for a significant downregulation of SMVT expression. This, especially in combination, could be quite a factor given the usual x1000+ RDI vitamin B complex supplement dosages and biotin for hair-and-skin-marketing.
There are huge and powerful variations in human SMVT etc. expressions and what I still haven't read figured out is why it is that always only two-thirds of those with recognized significant genetic homozygotous or heterozygotous mutations get their symptoms relieved by supraphysiological PA+Biotin supplementation (to allow for passive uptake via dissusion),
and why some few others with the same (mild) mutations may even remain symptom-free.