Multiple Sclerosis and Propionic Acid: A Potential Treatment?

I’ve illustrated this post with a picture of Janus, the Roman god of, among other things, duality.  Every time I read about short chain fatty acids (SCFAs), I think of him.

Over the years, I’ve written about the benefits of SCFAs many times. (Here’s just one of many such examples.) I’ve also written about the massive amount of research that suggests that too much of a good thing, including SCFAs, are neurotoxic and extremely detrimental to health.  (For example, here.)

I’ve commented before about how I find this idea of balance particularly interesting.  SCFAs are critically important for good health as long as you have the right amount; and to make this even more complex, the timing is critical:  they are good in the right amount at the right time.  Just as excess levels are associated with disease, so are low levels. Since SCFAs are produced by gut bacteria, it’s easy to imagine how alterations in the microbiota can alter levels of these metabolites to influence the development of various illnesses.

The human biome is insanely complex.

A week ago or so, a paper was published in the journal, Cell, which explored how propionate (also called propionic acid, or PPA) “shapes” the course of multiple sclerosis (MS) by influencing the immune system.[i]

Like other autoimmune diseases, MS involves an increase in inflammatory immune cells and a decrease in regulatory ones (Treg, which modulate inflammation).  This hyper inflammatory response leads the body to mistakenly attack the myelin sheaths of nerve fibers, which is a protective layer surrounding the nerves.  This hampers the ability of nerves to send and receive signals properly.

In this study, the blood and stool of almost 300 people with MS were examined:  the results showed low levels of PPA, no matter what type of MS the person had (i.e. relapsing-remitting, progressive, etc.)  The bacterial species which produce PPA were  found at lower levels; bacterial species associated with disease, like Shigella, were found to be at higher levels.  The microbiome composition of the MS patients also varied according to the course of their disease, and this paralleled the fact that those newly diagnosed had the lowest levels of PPA, “…indicating that alterations in the gut microbiome might affect the severity of MS and that successful interventions might involve restoration of gut homeostasis.”

Thus, these scientists hypothesized that supplementing PPA, with its anti-inflammatory capabilities, might have a beneficial effect on those with MS, the hope being that the metabolite could boost levels of regulatory cytokines.  91 patients and 24 controls were given 1000 mg of PPA daily for 14 days.  After these 2 weeks, Treg (including IL-10, one of the most important) rose by 25% in the control group and by 30% in the MS patients.  52 patients continued to take the PPA after the study concluded, and the improvement in Treg remained.  This experiment was repeated in a 2nd group of patients and the results were the same.  To boot, high levels of pro-inflammatory immune cells dropped significantly.

Long-term PPA supplement use was also studied.  41.2% of those on PPA had a lower  annual relapse rate; 47.4% had a stable relapse rate; 11.3% had an increased rate of relapse.  And one more interesting finding:  22 patients, who remained on the PPA for a year and a half, underwent brain MRIs: “…the striatum, a region known to shrink (brain atrophy) in MS, actually increased in volume compare to scans taken before starting this treatment.”[ii]   This correlated with an improvement in clinical symptoms:  “This improved Treg cell function correlates with alleviation of clinical symptoms in MS patients. In a retrospective setting, we observed a decrease in relapse rate and stabilization of disability during long-term [propionic acid] supplementation.”

By the way, no adverse effects to the PPA supplementation were reported.

The researchers conclude that their study saying that it “…provides further evidence of the hypothesis that SCFAs are reduced in autoimmune diseases, such as MS, as a consequence of an altered gut microbiome.… [PPA] supplementation had a beneficial effect on immunological, neurodegenerative, and clinical parameters in MS patients, including relapse rate and disability progression.”

This is very preliminary research, so rest assured, I will follow it.  This this may well apply to other autoimmune diseases and help many people.


[i] Duscha, A, et. al. Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism.  Cell. 2020;180(6):1067-1080.


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