dietary propionate can alleviate Parkinson’s disease symptoms

[Farooqji]

scitechdaily.com/scientists...

[JayPwP]

Excellent news. Where to buy and how to take?

Link to research

cell.com/cell-reports/fullt...

park_bear your thoughts please?

[park_bear in reply to JayPwP]

I regard the headline here as misleading because this was from a flatworm study so its applicability to humans is unclear.

Recent studies have shown that there is less propionic acid in Parkinson's patients' plasma than healthy patients. So it's possible that propionic acid supplementation could benefit Parkinson's patients. Calcium and sodium propionate are readily available as food additives and propionic acid is available as a chemical. However this is not without risk:

drc.bmj.com/content/9/1/e00...

Acute effects of the food preservative propionic acid on glucose metabolism in humans

Results: PA, as compared with placebo, significantly increased: (1) glucagon and norepinephrine during protocol 1; (2) glucagon, norepinephrine, and epinephrine under euglycemic conditions in protocol 2; and (3) norepinephrine, epinephrine, and EGP under hypoglycemic conditions in protocol 2.

Conclusion: Oral consumption of PA leads to inappropriate activation of the insulin counterregulatory hormonal network. This inappropriate stimulation highlights PA as a potential metabolic disruptor.

nature.com/articles/s41598-...

Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder

"We investigated the effect of Propionic acid (PPA), a short-chain fatty acid (SCFA) and a product of dys-biotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation and inflammation....Following 2 mM PPA exposure, TNF-α transcription increased 4.98 fold and the cytokine increased 3.29 fold compared to control ... the data supports a significant role for PPA in modulating hNSC patterning leading to gliosis, disturbed neuro-circuitry, and inflammatory response as seen in ASD"

Not sure how 2 millimoles compares to realistic physiological concentrations. It seems high but cannot say that I know.

[JayPwP in reply to park_bear]

Aren't propionate and propionic acid different molecules?

[park_bear in reply to JayPwP]

Propionate refers to the calcium or sodium salt of propionic acid. The first study that I referenced, which referred to propionic acid in the title, actually used calcium propionate as the test substance:

"We performed a randomized, placebo-controlled, crossover study in 28 healthy men and women to determine the effect of PA (1500 mg calcium propionate) "

They are biologically equivalent because they ionize in solution.

[JayPwP in reply to park_bear]

Thank you 🙏

[LAJ12345]

but this

ncbi.nlm.nih.gov/pmc/articl....

“ One example of the effects of excess propionate is propionic acidemia (PA). This metabolic disorder has been associated with motor impairments, brain atrophy, cognitive impairments, and dementia (Sethi et al., 1989; Morland et al., 2018; Schwoerer et al., 2018).”

[MSMN]

As far as I know you can increase propionate production in the gut by increasing foodintake that stimulates the formation of butyric acid : fermented guar fibre (powder, is a supplement - use it daily and take a lot of it but start slowly) and ghee, grassfed butter.

[chartist]

Keeping things in context, that is a 2024 study utilizing a flatworm. In the following 2021 study it is suggested that increased propionate via administration of osteocalcin intraperitoneal injection to a PD mouse model helped to ameliorate motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model as discussed here :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant study quote :

' The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice. '

Inulin also has been shown to significantly increase propionate while reducing the Bacteroidetes/Firmicuties ratio.

In the following study it is shown that the prebiotic, Inulin , significantly increased the level of propionate in the gut of humans :

gut.bmj.com/content/64/11/1744

Here are two relevant quotes from the human study :

' We have estimated that 10 g inulin-propionate ester ingestion leads to a 2.5-fold increase in daily colonic propionate production, a level very difficult to achieve through feeding a mixed fermentable fibre diet.20 We also demonstrated that ingestion of the inulin-propionate ester increases plasma propionate levels. '

' We subsequently, in the first-in-human studies, demonstrated that increased delivery of propionate to the colon acutely modulates gut hormone release and reduces food intake in healthy subjects. '

It is just my opinion, but it seems that a flatworm study is much less relevant now, given the prior existence of the PD mouse model study which had already shown the benefit of propionate for the purpose.

Although neither study assures effectiveness in humans it seems that the above information in conjunction with the very good safety profile of the prebiotic fiber, Inulin, seems like a more appropriate study for 2024 would have been a human study utilizing at least 10 grams / day of Inulin in PwP to see what benefit if any it may offer. Unfortunately, those study dollars may have been wasted on the flatworm study which seems wasteful IMO, given the prior existence of the 2021 PD mouse model study illustrating the usefulness of propionate in this model.

Art

[Reetpetitio in reply to chartist]

Hopefully this proof of concept study in humans will be followed up by a larger trial -

ncbi.nlm.nih.gov/pmc/articl...

[Rufous2 in reply to Reetpetitio]

Thanks for posting this. Interesting paper that made me aware of a prebiotic I'd not heard of before.

"Resistant maltodextrin and inulin produced the greatest increase in total SCFA levels followed by resistant starch and rice bran (Fig. 2b and Supplementary Table S1). Each fiber type had a distinct metabolic signature: resistant starch was highly butyrogenic, resistant maltodextrin was highly propiogenic, and inulin and rice bran promoted the production of all three SCFA."

I found one source of "resistant maltodextrin." It's expensive, but might be worth it for those who want to try to recreate the fiber blend used in the study you linked;

amazon.com/Fiber-Fibersol-D...

[Rufous2 in reply to chartist]

Art, one of your quotes said;

"We have estimated that 10 g inulin-propionate ester ingestion leads to a 2.5-fold increase in daily colonic propionate production, a level very difficult to achieve through feeding a mixed fermentable fibre diet."

I've used inulin for many years, but had never heard of "inulin propionate ester." Digging a bit I found this;

"In order to make Inulin Propionate Ester (IPE), you need two compounds; inulin and propionate. Inulin is a naturally occurring fibre that can be found in a variety of plants, but industrial quantities are derived from chicory, a plant which belongs to the dandelion family.

Propionate on the other hand is a short chain fatty acid (SCFA), which is produced in the gut through its microbiome. That is, the bacteria in our intestines will use the fibre we eat to produce propionate. IPE then is created by combining these two compounds through a special bond known as an “ester bond”.

The compound IPE was created for three reasons:

1. To help deliver more propionate directly to the colon

2. To help deliver more inulin to the colon

3. To help support appetite suppression and feelings of fullness

The ester linkage of the Inulin Propionate Ester will be broken down by the gut bacteria, releasing the propionate to work its magic. The inulin portion will also be gobbled up by the bacteria, releasing more short chain fatty acids such as propionate." mrsupplement.com.au/inulin-...

So it seems this form of inulin doesn't just rely on bacteria to turn it into propionate, but actually delivers propionate directly to the gut, which is why they were able to achieve such high levels in their test subjects. Seems like this could be very important to those whose guts are low in propionate producing bacteria. Unfortunately, I haven't been able to find a source for inulin propionate ester, so if you or anyone else can direct me to one, I'd be grateful.

[chartist in reply to Rufous2]

I haven't seen this form of inulin previously. I take high dose melatonin at 132 mg/day which has been shown to increase SCFAs in the gut and I think that combined with inulin intake should be useful for me. If you want to add further to propionate levels, beta glucan may be useful, but too high of a propionate level may not be healthful.

Art

[JayPwP in reply to Rufous2]

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