Experience with B5 supplementation?

[AkunaMatata]

Noticed this rather serious paper from last year in the Journal of Parkinson's Disease: Localized Pantothenic Acid (Vitamin B5) Reductions Present Throughout the Dementia with Lewy Bodies Brain ( content.iospress.com/articl... )

"Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum."

They note:

"Despite the rarity of pantothenic acid deficiency, significantly lower levels of dietary pantothenic acid intake have been observed in individuals with PD in comparison to healthy individuals, with pantothenic acid levels displaying clinical importance in predicting the incidence of PD [23]; in this study, UPDRS scores were also negatively correlated with pantothenic acid intake. As such, decreased dietary pantothenic acid intake may be associated with both PD incidence and severity. Pantothenic acid intake has also been associated with amyloid-β burden in individuals with mild cognitive impairment (MCI), indicating a potential link with AD [24]. As such, despite a lack of outright pantothenic acid deficiency, supplementation may be a potential therapeutic option for the treatment of these neurodegenerative diseases."

"Non-CNS disturbances in pantothenic acid and related pathways have also been observed in neurodegenerative diseases; for instance, pantothenate and CoA biosynthesis has been found to be disturbed in LC–MS metabolomics analyses of PD and healthy plasma and serum samples, with decreased pantothenic acid levels observed even in the early stages of PD [27, 28]. The presence of pantothenic alterations in the PD gut is disputed, with some studies showing no changes in stool sample levels [29] while others have shown decreases [30], and with another study showing positive associations between fecal pantothenic acid levels and non-motor symptoms in PD [31]. Both increased and decreased serum pantothenic acid levels were reported in a study of 50 individuals with non-specific dementia [32], and pantothenate and CoA biosynthesis pathway dysregulation has been reported in a multi-omic investigation of the AD brain, blood, and cerebrospinal fluid [33]. As such, pantothenic acid disturbances may be a wider, multi-system issue that does not only affect the brain in neurodegenerative diseases; if so, this could make the administration of pantothenic acid supplementation a more straightforward and viable option for therapeutic trials."

Has anyone tried supplementing with B5?

Pantethine is another form of B5: “Although pantethine is considered the more biologically active form of vitamin B5, it is less stable than pantothenic acid and tends to degrade over time if it is not kept refrigerated” ( alzdiscovery.org/uploads/co... )

[Esperanto]

Thank you for bringing this research about B5 pantothenic acid to our attention! The potential role of B5 in PD and dementia with Lewy bodies underscores again the importance of ALL the individual B vitamins, which have been discussed more frequently in CP posts last years. This raises important questions about dietary intake and supplementation.

I wanted to emphasize the significance of the entire B complex. Each B vitamin has a unique function, and they work synergistically. Supplementing with a moderate-dose B complex or multivitamin could be a wise alternative to taking individual B vitamins separately. This approach may enhance their overall effectiveness and support brain health more comprehensively.

In my experience, this perspective on moderate complete supplementation has yielded very good results. I will soon be updating the overview of B complexes and multivitamins. I welcome any suggestions and new options.

healthunlocked.com/cure-par...

[AkunaMatata in reply to Esperanto]

I don't know if all B vitamins are equally useful. People should first test their serum levels before supplementing. You can't improve what you don't measure. And the form and dose matter a lot:

B1: benfotiamine seems better.

B5: unclear if pantethine or calcium pantothenate is best. Higher might be better in terms of dose.

B6: pyridoxal-5′-phosphate (P5P). Medium and high doses are dangerous.

B9: not sure if it's useful. Depends on your age: "A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging." ( life-science-alliance.org/c... )

B12: methylcobalamin. Higher dose is probably better.

Etc.

The devil is in the details.

[JayPwP in reply to AkunaMatata]

Each person's dose will vary and will need multiple B-Complex testing till stabilization of the dose.

Also B-Complex products usually come preformulated which is very difficult to customize.

[bookish in reply to AkunaMatata]

The Bs are certainly complicated. Serum levels can be misleading as they can be high although in cellular deficiency due to transport failures etc. B6 as P5P is generally far less problematic than (inactive) pyridoxine, which competitively inhibits the active form. B9 can be hugely useful in the right form for the individual - folic does nothing for me except put my serum up to top of range, whereas methyltetrahydrofolate stopped a number of symptoms (I don't have PD) and my serum level went down to mid range. And B12 can be vastly complex, both to test and treat. Injections are the only certain way to treat, as oral/sublingual etc are not reliable for all and you have no idea if they are ok for you until you see the difference. Oral etc can raise blood levels without correcting and starting repair of neurological damage. It can slow progression, from my own experience, but not start to reverse it as injections do. Some even with pernicious anaemia cope with very high sublinguals, but over time this is likely to become less effective. I've been using a low dose of pantothenic (as calcium pantothenate) for some years, so this is very interesting. Cheers

[park_bear in reply to AkunaMatata]

It is the pyridoxine form of B6 that is toxic in quantity, not P5P. Details here: healthunlocked.com/cure-par...

[AkunaMatata in reply to park_bear]

Thanks, I didn't know!

[Steegen]

The pantethine form of B5 you mentioned, was thought to be a promising avenue for PD a while back, if I recall correctly.

[AkunaMatata in reply to Steegen]

Hum, I didn't find anything about that, it seems to be a rather recent hypothesis. All I could find is: nature.com/articles/s41467-... "Previous studies revealed D-pantethine (D-pan), a close relative of vitamin B5 (pantothenate) and a metabolic substrate for CoA synthesis, could bypass PANK in CoA synthesis in a currently unclear biochemical pathway, and nicely rescue multiple animal PKAN models"

[Steegen in reply to AkunaMatata]

I can do a deeper dive later, but this was probably the study I was thinking of. It was a mouse study from 2010:

"We found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH) production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals."

link.springer.com/article/1...

I think there are also some studies on it benefitting Alzheimers in mouse models.

I was interested to see that in the study you linked, the researcher has investigated a few different neurodegenerative diseases that appear to involve B5 deficiency, and even hypothesised it might be a common feature of neurodegenerative disease.

[AkunaMatata in reply to Steegen]

Thanks. Mouse study MPTP model: this has close to zero value.

Yes for AD some people looked at it: alzdiscovery.org/uploads/co... (last updated in 2019 so pretty old)

[Steegen in reply to AkunaMatata]

Yeah fair enough. Perhaps the mouse study adds a bit of value when taken in combination with the other research (PKAN, Alzheimer's, the B5 deficiencies in PDD brains etc).

But I agree, it's not much on it's own. I thought there was more on pantethine, I might just be mistaken.

[AkunaMatata in reply to Steegen]

There's not a lot but if you "connect dots" there's enough to warrant further research (or self experimentation / biohacking?):

researchsquare.com/article/...

nature.com/articles/s41531-... ("The decreased levels of pantothenic acid in PD patients have been found in the plasma, serum, fecal and brain tissues of PD patients. It was reported that pantothenic acid may associate with the neurodegenerative inflammation and oxidative stress in PD through the brain-gut axis. However, metabolic modeling of the human gut microbiome predicted increased secretion of pantothenic acid in the human gut microbiota, which is the converse of the changes in clinical studies of PD. Besides, pantothenic acid is a necessary precursor for coenzyme A (CoA) synthesis. CoA is a carbon transporter, required for pyruvate to be converted to acetyl-CoA before the citric acid cycle. The decreased levels of pantothenic acid may reflect the energy dysfunction in PD patients.")

mdpi.com/2076-3425/13/7/1119 (“Dietary intake of pantothenic acid was negatively correlated with PD severity and symptoms of motor examination and complication.”)

Coenzyme A fueling with pantethine limits autoreactive T cell pathogenicity in experimental neuroinflammation: link.springer.com/article/1... (for MS, not PD, but might still be relevant)

It's also studied for heart failure: onlinelibrary.wiley.com/doi... ("“If restoring energy balance in HF by boosting CoA levels ameliorates clinical outcomes, and enhances patients' quality of life and potentially duration of life, Pan, pantethine, or PPanSH could complement conventional treatments with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, and mineralocorticoid-receptor antagonists targeting mainly dysregulation in the neurohormonal system or reducing cardiac workload.")

The only question to me is: pantethine or pantothenic acid?

[Steegen in reply to AkunaMatata]

Very interesting, thanks for posting.

I assume you've seen this topic already?

"Pantothenic acid deficiency may be the cause of parkinsons"

healthunlocked.com/cure-par...

[AkunaMatata in reply to Steegen]

Thanks. It seems unlikely that B5 deficiency would be the cause. But it might still have symptomatic or even neuro-protective benefits. Especially if combined with other interventions.

[park_bear in reply to AkunaMatata]

Indeed, most MPTP mouse studies are worthless because the test treatment is applied before or with the toxicant, preventing the toxic cascade that will progress to Parkinson's, if allowed to continue. At this stage even a simple antioxidant will be effective. Such is the case with this study: "Mice received two 5-day treatments with daily i.p. injections of 15 mg of pantethine, before and after 2'-methyl-MPTP administration." Further discussion here: healthunlocked.com/cure-par...

Researchers who are serious will allow the animal to progress to Parkinson's first, before applying the test substance. Often they will use the A53T mouse, genetically engineered with a human mutation that causes Parkinson's. These studies are of value because they are evidence of efficacy for treatment of Parkinson's. One example: healthunlocked.com/cure-par...

[LAJ12345]

my husband has been taking pantethine for a few years now

nz.iherb.com/pr/now-foods-d...

[AkunaMatata in reply to LAJ12345]

Did he notice anything from taking pantethine 600 mg?

[Sydney75]

Before my HWP diagnosis we did a micronutrient panel that looks back in your blood 3 months he was very low in B5. At that time we did not associate it with PD, used supplements to increase levels. DatScan gave us the diagnosis. He was also low in choline prior to diagnosis. He did have some cognitive issues and major anxiety.