Lipoic acid for multiple sclerosis
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What is lipoic acid for MS?
Lipoic acid, also known as alpha lipoic acid, is an antioxidant molecule, made naturally in the body and also found in foods, that is being explored as a potential therapy for relapsing and progressive forms of multiple sclerosis (MS).
Found in cells, lipoic acid helps turn glucose (blood sugar) into energy.
The compound is available in over-the-counter dietary supplements.
Therapy Snapshot
| Treatment name: | Lipoic acid |
| Administration: | Being tested in MS in oral tablet formulation |
| Clinical testing: | In Phase 2 trials for PPMS and SPMS |
How does lipoic acid work in MS?
In MS, the immune system erroneously launches an inflammatory attack against myelin, a fatty substance that wraps around nerve fibers and is key for effective nerve communication.
Once the immune system has caused initial damage in MS, oxidative stress then becomes another driver of the disease. Oxidative stress is a type of cellular damage that results from an imbalance between the production and clearance of potentially harmful oxidant molecules.
Lipoic acid is a powerful antioxidant that is found in very small amounts in foods such as spinach and broccoli, and is also produced naturally in the liver. This compound is able to eliminate the harmful reactive molecules that build up in MS, preventing them from causing oxidative stress.
In addition to its antioxidant properties, mouse models and data from human trials have shown that lipoic acid lowers several markers of inflammation and reduces the number of inflammatory immune cells that migrate into the brain and spinal cord.
Together, these mechanisms could help lessen the immune attack that drives MS and alleviate neurological symptoms of the disease.
How will lipoic acid be administered in MS?
Lipoic acid is available as an oral formulation or as an intravenous, or into-the-bloodstream, injection. In MS clinical trials, the therapy has mostly been tested in the form of oral tablets or capsules, at a daily dose of 1,200 mg.
Lipoic acid in MS clinical trials
Lipoic acid has been studied in several MS clinical trials, most of which were small studies enrolling fewer than 100 patients.
Pilot trial
An early pilot trial investigated three different doses of lipoic acid capsules — 600 mg twice daily, 1,200 mg once daily, or 1,200 mg twice daily — against a placebo over two weeks. The study enrolled 37 patients with relapsing and progressive forms of MS, including relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).
In this trial, the treatment was overall well tolerated, and both 1,200 mg doses lowered markers of inflammation associated with immune cell migration into the brain and spinal cord.
Phase 1 trial
A later Phase 1 trial (NCT00997438) was conducted by the Portland Veterans Affairs Medical Center in collaboration with the Oregon Health and Science University. It tested the safety and pharmacological properties of lipoic acid capsules in people with RRMS and SPMS, and in healthy volunteers. In total, the study enrolled 57 participants who received a single 1,200 mg dose of the antioxidant.
Results showed that the medicine’s pharmacological properties were similar in people with or without MS, and that it was generally well tolerated, with no serious adverse events reported.
Phase 1/2 trial
A more recent Phase 1/2 trial (NCT02133664), conducted at Oregon Health in collaboration with the National MS Society, investigated a combination of lipoic acid plus omega-3 fatty acids in 54 adults with RRMS or SPMS.
Patients were randomly assigned to take daily supplements of 1,200 mg lipoic acid along with omega-3 fatty acids (fish oil concentrate), or a placebo, for 12 weeks, or about three months. The main goal of the study was to determine whether the supplement treatment would improve measures of cognition.
The study results showed no significant differences in cognitive outcomes at 12 weeks between patients given supplements or the placebo.
Phase 2/3 trial in RRMS
The Iran University of Medical Sciences conducted a Phase 2/3 clinical trial (IRCT138812222602N2) to investigate oxidative and immune system changes after treatment with lipoic acid. A total of 52 adults with RRMS were assigned to receive lipoic acid capsules at a daily 1,200 mg dose, or a placebo, for 12 weeks.
Overall, participants given the supplement showed a significant increase in total oxidative capacity in their blood, and a significant decrease in levels of certain pro-inflammatory markers. Notably, disability outcomes, as assessed via the Expanded Disability Status Scale (EDSS), did not differ between patients given supplements or the placebo, when examined at 12 weeks.
Phase 2/3 trial in non-active SPMS
A Phase 2/3 trial (NCT01188811), conducted at the Veterans Affairs Portland Health Care System and Oregon Health, investigated a daily dose of 1,200 mg lipoic acid, versus a placebo, in people with non-active SPMS. Non-active status was defined as no relapses in the prior five years. A total of 51 patients were included in the trial, which lasted about two years.
The trial met its main goal, which was to determine if lipoic acid could significantly prevent the loss of brain volume (brain atrophy) after two years. Over the duration of the trial, patients given a placebo lost, on average, 0.65% of their brain volume per year. That rate was reduced to 0.21% per year with lipoic acid. Participants treated with lipoic acid also tended to have better walking function, though the difference was not statistically significant.
Lipoic acid was generally well tolerated; the most common side effect associated with the medication’s use was gastrointestinal upset. One participant experienced a serious side effect, vomiting and dehydration that required hospitalization, that was deemed related to treatment. The side effect was resolved upon stopping the supplements.
Ongoing trials
A study called LAPMS (NCT03161028), sponsored by the VA Office of Research and Development, is underway at multiple sites in the U.S., and one in Canada. This Phase 2 clinical trial is investigating lipoic acid in patients with progressive forms of MS, including PPMS and SPMS.
The trial enrolled about 115 adults who were randomly assigned to 1,200 mg of lipoic acid, or a placebo, taken orally once per day, for two years. The main goal is to evaluate the effect of the supplements on walking ability, measured via the Timed 25-Foot Walk. Brain atrophy and falls also will be assessed.
Common side effects of lipoic acid in MS
The most common side effects associated with lipoic acid in MS clinical trials include:
- reactions affecting the skin, such as rash
- gastrointestinal problems, including nausea, vomiting, and abdominal pain
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about lipoic acid in MS
Lipoic acid is an antioxidant molecule that is available as a nutritional supplement, and is being investigated as a potential treatment for multiple sclerosis. As an antioxidant, lipoic acid can lower the amount of toxic oxidative molecules that contribute to MS and other neurological diseases. Data also suggests that lipoic acid can reduce the number of inflammatory immune cells that enter the nervous system, and that it may have other immune-modulating properties that could reduce the autoimmune attack that drives MS.
In the U.S., lipoic acid is marketed as a dietary supplement. The U.S. Food and Drug Administration regulates such supplements as food, not medication. This essentially means that lipoic acid can be sold in the same way that any food would be, so long as it is properly produced and labeled. In multiple sclerosis, the therapy has shown promising results in Phase 2 and Phase 3 trials in multiple forms of the disease, but it may still take several years before lipoic acid gains a potential FDA approval as a treatment for the condition.
Clinical trials testing lipoic acid in multiple sclerosis have not included participants who were pregnant or breastfeeding, so it is not known if the supplement is safe for use in these individuals.
In a Phase 2/3 clinical trial that enrolled 52 adults with relapsing-remitting multiple sclerosis, treatment with lipoic acid significantly increased the clearance of harmful oxidative substances and lowered markers of inflammation within 12 weeks. However, it remains unclear when the first signs of efficacy begin to be observed in people with multiple sclerosis.
Neither hair loss nor weight gain has been reported as a side effect of lipoic acid in multiple sclerosis clinical trials. However, data from clinical trials in other conditions have suggested that taking lipoic acid may lead to a reduction in body weight.
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