Higher bile acid levels in blood linked to slower MS progression
Supplements found to be safe, well tolerated in progressive MS in study
Higher blood levels of bile acids — molecules found in the digestive fluid bile, which helps absorb fat in the gut — are associated with a slower progression of multiple sclerosis (MS), as indicated by imaging scans, a study by U.S. researchers reported.
In a small clinical trial in people with progressive forms of MS, daily oral supplementation with a bile acid called tauroursodeoxycholic acid, or TUDCA, lowered the blood levels of certain pro-inflammatory immune cells.
Such supplements did not significantly improve clinical outcomes compared with a placebo. However, that likely was due to a short treatment period and follow-up, the researchers noted, while calling for further study.
“TUDCA supplementation in [progressive MS] is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration,” the researchers wrote.
The study, “Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease,” was published in the journal Med.
Investigating impact of bile acid supplementation on MS progression
MS is a neurodegenerative disease in which the immune system causes damage to certain parts of the brain and spinal cord. This faulty immune response is directed against myelin, a fatty coating around nerve fibers that boosts the speed of electrical signals.
Bile acids are molecules generated in the liver that mainly help the digestive system absorb fats, or lipids. But they can also modulate certain metabolic processes and interact with receptors found in cells in the brain and immune system.
Research has shown that multiple sclerosis patients, mainly those with progressive MS, have lower blood levels of bile acid metabolites. Meanwhile, animal studies have suggested that supplementation with bile acids can offer some protection and ease disease severity.
However, how bile acid supplements impact people with the disease is unknown, according to a team of researchers at the Johns Hopkins University School of Medicine in Maryland.
To learn more, the team first examined whether bile acid levels correlated with measures of disease progression in MS patients. The analysis included 107 patients with available MRI brain scans, and 192 who underwent repeated retinal scans using optical coherence tomography, or OCT.
The results showed that higher levels of primary bile acids — those synthesized in the liver — at the study’s start were associated with significantly slower shrinkage, or atrophy, across the whole brain, and in various regions within the brain over time.
In the OCT group, patients with higher primary bile acid levels when the study started, or at baseline, had significantly slower atrophy in a region of the eye called the outer nuclear layer, which contains the cell bodies of photoreceptors, or those that collect light.
“Overall, these data demonstrate that baseline levels of circulating bile acid metabolites are associated with subsequent MS progression based on imaging metrics,” the researchers wrote.
Larger studies needed into effects of TUDCA bile acid supplements
Building on these findings, the team conducted a small Phase 1/2 clinical trial (NCT03423121) to test the impact of TUDCA in adults with progressive forms of MS. In total, 26 people with primary progressive MS (PPMS) and 28 with secondary progressive MS (SPMS) — 54 patients in total — were randomly assigned to receive 1 g of oral TUDCA twice daily or a placebo for about four months.
According to previously reported data, supplemented patients experienced significant increases in TUDCA blood levels as well as in levels of several other bile acids, as expected. In addition, TUDCA significantly reduced several types of immune T-cells versus the placebo, and altered the composition of microbes in the gut. These are known as gut microbiota.
However, TUDCA supplementation had no significant effect on several clinical outcome assessments, the data showed.
“It is likely that a larger follow-up trial with a longer duration would be necessary to accurately assess the effects of TUDCA supplementation on clinical measures of disease severity,” the team wrote.
We show that circulating bile acid metabolites predict MS disease progression. … Oral TUDCA supplementation is safe and tolerable in people with progressive MS and results in increased circulating bile acid levels.
Regarding safety, TUDCA was safe and well tolerated. Gastrointestinal side effects, such as nausea, vomiting, diarrhea, reflux, and abdominal pain, were the most commonly reported among patients given supplements.
“We show that circulating bile acid metabolites predict MS disease progression,” the researchers concluded. “Oral TUDCA supplementation is safe and tolerable in people with progressive MS and results in increased circulating bile acid levels, altered [T-cells] and the gut microbiota.”
Limitations cited by the researchers were the study’s short duration and the small number of patients involved.
“Future studies with a larger sample size and longer duration are needed to validate these preliminary findings and to better assess the effects of TUDCA supplementation on clinical and imaging outcomes in people with MS,” the team wrote.
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