Antioxidant lipoic acid slows brain atrophy in progressive MS: Study
But it failed to lessen symptoms or improve walking in 2-year trial
- In a clinical trial spanning two years, lipoic acid was shown to slow brain atrophy in people with progressive multiple sclerosis.
- However, the antioxidant failed to ease symptoms such as fatigue.
- More research is now being conducted in the global clinical trial Octopus.
In people with progressive multiple sclerosis (MS), treatment with the antioxidant lipoic acid did not improve walking or lessen other symptoms, such as fatigue, but it did show signs of slowing brain atrophy, or the loss of brain tissue.
According to the researchers, this suggests possible positive biological effects from the antioxidant’s use, despite no clear clinical benefit.
These are the main takeaways from new data from a Phase 2 clinical trial (NCT03161028) that tested lipoic acid against a placebo over two years (24 months) in more than 100 adults with progressive MS. The trial assessed how safe the antioxidant was when taken as oral capsules daily and how well it works compared with the placebo.
The researchers noted that lipoic acid does not easily cross the blood-brain barrier that controls which substances can pass from the bloodstream into the brain, limiting how much reaches the nervous system. Nonetheless, brain volume did not decrease in patients treated with the antioxidant, the data showed.
“It didn’t work clinically in progressive [MS] the way we hoped,” Rebecca Spain, MD, an associate professor of neurology in the Oregon Health & Science University (OHSU) School of Medicine in Portland, who led the study, said in a university news story that detailed the findings.
“However, the slowing of brain atrophy that we saw in MRI images suggests that we may yet be on the right track, especially if we can find a better way to deliver the beneficial effects of an antioxidant like lipoic acid,” said Spain, who also codirects the Veterans Affairs MS Center of Excellence West.
The study, “Lipoic Acid for Treatment of Progressive Multiple Sclerosis A Phase 2 Randomized Clinical Trial,” was published in the journal Neurology. The work was funded in part by the U.S. Department of Veterans Affairs, the National MS Society, and the MS Society of Canada.
MS is a chronic disease in which the immune system damages myelin, the protective coating around nerve fibers in the brain and spinal cord. Over time, the underlying nerve fibers can also become damaged. Progressive forms of MS worsen steadily, leading to increasing disability for patients.
Mixed results seen in trial testing lipoic acid in 115 MS patients
Lipoic acid — which helps turn blood sugar, or glucose, into energy in the body’s cells — is found in small amounts in foods and over the counter supplements. It is also produced in the body by the liver.
It reduces oxidative stress, which occurs when the production of harmful reactive molecules exceeds the body’s ability to neutralize them with antioxidants. It also reduces inflammation and limits the entry of immune cells into the brain and spinal cord.
Building on earlier data that lipoic acid may protect the brain, Spain’s team randomly assigned 115 adults with primary or secondary progressive MS to receive a daily dose of either 1,200 mg of the antioxidant or the placebo. The participants had been diagnosed with MS for an average of 16.3 years, and slightly more than half (56%) were on disease-modifying medication.
The study’s primary outcome was walking speed, assessed by the Timed 25-Foot Walk. This test, which measures how quickly someone can walk a short distance, is used to monitor physical decline in MS.
The results showed that lipoic acid did not enhance walking speed compared with the placebo.
Similarly, there were no significant differences in mobility, other neurological exams, or patient-reported symptoms, such as fatigue or daily functioning.
MRI scans showed signs of slowed brain loss with antioxidant’s use
However, MRI scans showed that whole-brain volume appeared relatively stable in patients given the antioxidant, while it tended to decrease in those in the placebo group.
The effect was significant in the deep gray matter, which is typically most severely affected in MS. The volume of deep gray matter remained stable in patients taking lipoic acid but was lessened in the placebo group. These findings suggest possible neuroprotection, even without a clear clinical benefit, according to the researchers.
Even though the brain volume of people taking lipoic acid didn’t seem to decrease as much, the researchers found that the amount of scar tissue (called T2-weighted lesions) actually increased more in the lipoic acid group than in the placebo group. Nonetheless, those receiving the antioxidant still “demonstrated less whole-brain atrophy than the placebo [group], even after accounting for an increase in total [T2-weighted] lesion volume that occurred more in the [lipoic acid group],” the researchers wrote.
More patients stopped taking lipoic acid than the placebo, often due to unwanted side effects. Lipoic acid was linked to proteinuria, indicating an excess of protein in the urine — a sign that the kidneys may be damaged — which necessitated closer laboratory monitoring every three months.
In combination with this Octopus trial, we are going to learn more about whether lipoic acid is worth taking if you have progressive MS. … I am cautiously optimistic.
The data from this study are now being used in a larger U.K.-based research project called Octopus, for which Spain is serving as an adviser.
A multiarm, multistage clinical trial platform, Octopus will test lipoic acid and metformin, an antidiabetic also being explored as a potential MS treatment, against a placebo in a larger group of people with the progressive form of the disease.
“In combination with this Octopus trial, we are going to learn more about whether lipoic acid is worth taking if you have progressive MS,” Spain said. “I am cautiously optimistic.”
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