Lipoic acid shows limited benefit in progressive multiple sclerosis

The over-the-counter supplement lipoic acid may have a small beneficial effect in slowing the loss of gray matter in the brains of people with progressive forms of multiple sclerosis, according to new research led by Oregon Health & Science University and the Portland VA Health Care System.

However, the randomized controlled trial found that it did not improve the primary clinical outcome measured by walking speed. The findings were published Dec. 15 in the journal Neurology, the medical journal of the American Academy of Neurology.

The study included 54 participants with primary progressive and secondary progressive multiple sclerosis. People in the experimental group took a daily 1,200-miligram dose of lipoic acid over two years. Researchers compared the outcomes with 61 people who were given a placebo. They measured the primary outcome as walking speed. Secondary outcomes included brain atrophy measured by magnetic resonance imaging, or MRI, other clinical outcomes, and safety.

It didn't work clinically in progressive multiple sclerosis the way we hoped. 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."

Rebecca Spain, M.D., M.S.P.H., lead author, associate professor of neurology in the OHSU School of Medicine, co-director of the VA MS Center of Excellence West and staff physician at the Portland VA

Multiple sclerosis affects myelin, the protective sheath that covers nerve fibers in the central nervous system. Myelin and nerve fibers become damaged in MS, which slows or blocks electrical signals required for us to see, move our muscles, feel sensations and think. An estimated 2.8 million people worldwide have been diagnosed with MS.

Researchers hypothesize lipoic acid may have both anti-inflammatory and antioxidant effects that may protect damaged myelin and underlying nerves, assuming enough of it circulates in the blood to reach the brain.

"Lipoic acid is lipophobic," Spain said. "It does not cross the blood-brain barrier and get into the central nervous system very easily."

The study advanced a line of research that started with a mouse model, dose-finding studies and promising results from a pilot study published in 2017.

Participants in the trial used a relatively high dosage of lipoic acid, which can lead to unwanted side effects. For example, researchers at one point paused the OHSU study when they found two participants developed a kidney condition triggered by certain medications, including lipoic acid.

Researchers see reason for hope.

The study's findings are already being extended into a broader research project based in the United Kingdom called Optimal Clinical Trials Platform for Multiple Sclerosis, known as Octopus. That project is a multi-arm, multi-stage trial enabling researchers to test lipoic acid and metformin, another potential treatment for progressive MS, against a placebo in a much larger group of participants.

Spain, who is advising the U.K.-based initiative, said the global research initiative will combine OHSU's findings with other large datasets.

"In combination with this Octopus trial, we are going to learn more about whether lipoic acid is worth taking if you have progressive MS," she said. "I am cautiously optimistic."