Over-the-Counter Antioxidant Lipoic Acid Shows Mixed Results in Treating Progressive Multiple Sclerosis

A new clinical trial led by Oregon Health & Science University (OHSU) and the Portland VA Health Care System has taken a close look at whether an over-the-counter antioxidant, lipoic acid, could help people living with progressive multiple sclerosis (MS). The results are nuanced: while the supplement did not improve key clinical symptoms like walking speed, it did appear to slow the loss of gray matter in the brain, offering a possible hint of neuroprotective benefit.

The findings were published in the peer-reviewed journal Neurology and add an important piece to the ongoing effort to find effective treatments for progressive forms of MS, which remain among the most difficult neurological conditions to manage.

What the Study Looked At

The trial focused specifically on primary progressive MS and secondary progressive MS, two forms of the disease characterized by a steady worsening of symptoms rather than clear relapses and remissions.

Researchers enrolled 54 participants into the experimental group, who took a daily dose of 1,200 milligrams of lipoic acid for two years. Another 61 participants were assigned to a placebo group. This made the study a randomized controlled trial, the gold standard for testing medical interventions.

The primary outcome researchers wanted to improve was walking speed, a commonly used clinical measure in MS trials because mobility loss has a major impact on daily life. Secondary outcomes included changes in brain atrophy measured by MRI, other neurological assessments, and overall safety.

The Main Clinical Result: Walking Speed Did Not Improve

When the data were analyzed, the results were clear on the primary goal: lipoic acid did not significantly improve walking speed compared with placebo. In other words, people taking the supplement did not walk faster or show meaningful functional improvement in mobility over the two-year period.

This was a disappointment for researchers, as slowing or improving physical disability is one of the most urgent unmet needs in progressive MS. The study team openly acknowledged that the supplement did not deliver the kind of clinical benefit they had hoped for.

A Surprising Finding: Slower Brain Atrophy

Where the study became more interesting was in the MRI results. Participants who took lipoic acid showed a slower rate of gray matter loss in the brain compared with those on placebo. Gray matter is critical for processing information, controlling movement, and supporting cognition, and its loss is strongly linked to long-term disability in MS.

While this structural change did not translate into immediate clinical improvements, it suggests that something biologically meaningful may be happening in the brain. Researchers see this as a potential signal that lipoic acid could have a protective effect on nerve tissue, even if that effect is not yet strong enough to change daily functioning.

Why Lipoic Acid Was Considered in the First Place

Lipoic acid has long attracted interest because of its antioxidant and anti-inflammatory properties. In multiple sclerosis, inflammation and oxidative stress play major roles in damaging myelin, the protective sheath around nerve fibers, as well as the nerves themselves.

Earlier research laid the groundwork for this trial. The idea began with mouse models, followed by dose-finding studies and a small pilot study published in 2017, which suggested potential benefits. Those early results were encouraging enough to justify a larger, more rigorous clinical trial.

However, there is a significant challenge: lipoic acid does not easily cross the blood–brain barrier. That means even if it has beneficial properties, only a limited amount may actually reach the central nervous system, where MS-related damage occurs. This limitation may partly explain why clinical benefits were modest.

Safety Concerns and Side Effects

Because the trial used a relatively high dose of lipoic acid, safety was closely monitored. Most participants tolerated the supplement, but there were notable concerns.

At one point, researchers temporarily paused the study after discovering that two participants developed a kidney condition linked to certain medications, including lipoic acid. While these cases were rare, they highlighted that even over-the-counter supplements can carry risks, especially at high doses taken over long periods.

This finding reinforces the importance of treating supplements with the same caution as prescription drugs, particularly in vulnerable populations.

Why Progressive MS Is So Hard to Treat

Multiple sclerosis affects an estimated 2.8 million people worldwide. While treatments for relapsing forms of MS have expanded significantly over the past two decades, progressive MS remains much harder to manage.

In progressive MS, nerve damage continues even when inflammation is less obvious. This means therapies that work well for relapsing MS often fail to slow progression. As a result, researchers are increasingly focused on strategies that protect neurons directly, rather than only suppressing immune activity.

The lipoic acid study fits squarely into this broader effort to find neuroprotective approaches.

The Bigger Picture: What Brain Atrophy Really Means

One reason the MRI findings matter is that brain atrophy is a strong predictor of long-term disability in MS. Slowing brain volume loss is increasingly seen as an important marker of treatment success, even if short-term symptoms do not immediately improve.

That said, researchers caution against overinterpreting the results. A reduction in brain atrophy does not automatically mean better quality of life, especially if it does not lead to improved movement, cognition, or independence.

Still, many experts view this as a step in the right direction, particularly for a disease area with so few effective options.

What Comes Next: The Octopus Trial

The findings from this study are not the end of the story. They are already being folded into a much larger research effort in the United Kingdom known as the Optimal Clinical Trials Platform for Multiple Sclerosis, or Octopus.

Octopus is a multi-arm, multi-stage trial, designed to test several potential treatments simultaneously in a large group of people with progressive MS. Both lipoic acid and metformin, a widely used diabetes drug, are being evaluated against a shared placebo group.

This innovative design allows researchers to gather stronger evidence more efficiently and adapt the trial as results emerge. The OHSU study’s data will be combined with other large datasets, helping researchers better understand whether lipoic acid is truly worth pursuing.

What This Means for Patients Right Now

For people living with progressive MS, the takeaway is cautious. Lipoic acid is not a proven treatment, and it did not improve mobility in this trial. Anyone considering taking it should do so only after consulting a healthcare professional, especially given the potential side effects at high doses.

At the same time, the study provides a reason for measured optimism. It suggests that targeting oxidative stress and neurodegeneration could still be a viable path forward, even if lipoic acid itself turns out not to be the final answer.

Progress in progressive MS tends to come in small, incremental steps. This study adds valuable knowledge, rules out unrealistic expectations, and helps guide future research toward more effective strategies.

Research Paper Reference:
Lipoic Acid for Treatment of Progressive Multiple Sclerosis, Neurology (2025).
https://doi.org/10.1212/WNL.0000000000214454