Lipoic acid (also known as alpha lipoic acid) is an antioxidant available as an over-the-counter supplement taken by people with a variety of conditions, including HIV and diabetes. It is currently being studied as a potential neuroprotector for people with multiple sclerosis (MS).
In animal models of MS, lipoic acid has been shown to reduce inflammation and degeneration of the optic nerve and spinal cord.
How lipoic acid works
In MS, damage to the myelin sheath, the protective layer that surrounds nerve fibers, disrupts the transmission of nerve signals. This damage is thought to be caused by immune system cells, like T-cells, mistakenly attacking myelin. These cells move into the brain and spinal cord and begin to target myelin, leading to an inflammatory response.
The exact mechanism for lipoic acid as a treatment for MS is unknown, and the results of studies are mixed. It is believed that lipoic acid may have immunomodulatory (altering the immune response) and anti-inflammatory properties, both of which work against damage to nerves (neuroprotection).
There is evidence to suggest that lipoic acid may affect the signaling process that triggers the inflammatory response. A pilot study in people suggested it can reduce the number of T-cells that migrate into the brain and spinal cord, thus lessening the risk that they could attack and damage myelin. Lower levels were reported through measurements of biomarkers associated with T-cell migration into the brain and spinal cord. (Biomarkers are substances associated with a particular disease or response to treatment.)
Lipoic acid in clinical trials
The effects of lipoic acid has been studied in several clinical trials, mostly small studies.
An early pilot study compared oral lipoic acid given at different doses to 37 MS patients over a two-week period. The treatment was well-tolerated and appeared to reduce the level of T-cell migration into the brain and spinal cord. Results were published in the scientific journal Multiple Sclerosis in 2005.
A pilot study with 51 patients explored the effect of lipoic acid compared to a placebo in patients with secondary progressive multiple sclerosis (SPMS) over a two-year period. The results were positive, with the treatment reported to have reduced the speed of brain tissue loss and improved patients’ walking speed. Data were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress and the 68th annual American Academy of Neurology meeting in 2016.
A Phase 1 trial (NCT00997438) completed in 2016 aimed to assess the potential benefit of lipoic acid in patients with relapsing-remitting MS (RRMS) and SPMS, as well as observe how lipoic acid is broken down in the body in both MS patients and healthy participants. No serious adverse events or notable side effects were observed.
A Phase 2/3 trial (NCT01188811) to determine whether lipoic acid can protect the brain and slow disability in people with SPMS finished in 2016. Reported results showed a reduction in brain atrophy, suggesting it could play a neuroprotective role in SPMS. Lipoic acid was also found to be safe and well-tolerated; noted side effects were gastrointestinal.
A Phase 2 trial (NCT02133664), completed in 2017, aimed to determine whether lipoic acid and omega-3 fatty acids can improve cognitive function in RRMS or SPMS patients. Participants were randomly assigned lipoic acid and omega-3 fatty acids or a placebo for a period of 12 weeks. The ability to perform a range of cognitive tests was assessed at the start and end of the trial, and data compared. Results did not suggest that the treatment provides a significant benefit to cognition after 12 weeks.
A Phase 2 trial (NCT03161028) in progressive MS patients is planned but not yet enrolling participants. The U.S. trial aims to assess the neuroprotective capability of lipoic acid compared to placebo over two years. Neuroprotection will be evaluated through changes in measures of brain volume, as captured in magnetic resonance imaging (MRI) scans. Changes in mobility will also be evaluated using the timed 25-foot walk test and the 2-minute timed walk test.
The potential side effects of lipoic acid in MS have not been fully explored. Lipoic acid as a treatment for other conditions has been reported to cause headaches, sensations akin to pins and needles, skin rashes, and muscle cramps.
Lipoic acid has not yet been compared to current MS therapies in clinical trials, so its relative effectiveness is not currently known.
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