Antioxidant May Influence Brain Changes In Multiple Sclerosis, Study Suggests

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A small randomized trial of 36 people with mild to moderate multiple sclerosis linked N-acetylcysteine (NAC) treatment to changes in brain connectivity and glucose metabolism over about four months. Participants receiving NAC also reported improvements in several symptoms, but the study does not establish that NAC is effective MS treatment or clarify its longer-term benefits and risks.

A 36-person randomized trial found that people with mild to moderate multiple sclerosis who received N-acetylcysteine (NAC) alongside standard care had changes in brain connectivity and glucose metabolism on imaging, with reported improvements in several symptoms. The findings, reported at a neuroradiology meeting and published in IBRO Neuroscience Reports, are preliminary and do not show that NAC slows MS progression or should be used as a treatment.

The trial assigned 18 participants to NAC plus standard care and 18 to standard care alone. The NAC regimen combined weekly intravenous doses of 50 milligrams per kilogram with 500 milligrams taken orally twice daily on the other six days of each week. Both groups underwent PET-MRI assessments and completed symptom questionnaires at the start and again after four months, with the follow-up timing varying by two months.

Resting-state blood oxygen level-dependent functional MRI showed connectivity changes in the NAC group compared with the control group, including in the inferior frontal region, cerebellum, and parts of the temporal and parietal lobes. FDG PET scans showed increased glucose metabolism in several corresponding areas, including the inferior frontal and inferior temporal gyri. The report said participants’ self-reported cognitive and attention improvements correlated with imaging changes; that association does not establish that the imaging changes caused the reported benefits.

Only the NAC group showed statistically significant improvements from its initial scores on the reported measures: pain, fatigue, cognition, and attention. The reported P values were 0.015, 0.016, 0.036, and 0.010, respectively. The source does not provide effect sizes or enough detail to determine how large or practically meaningful those changes were. The researchers presented the work as an initial evaluation, rather than a definitive test of clinical effectiveness.

What the Imaging Changes May Show

The study examines whether targeting oxidative stress could complement existing approaches to MS, which commonly focus on inflammation. NAC is an antioxidant that can increase glutathione, a substance involved in the brain’s antioxidant defenses. The researchers said pairing functional MRI and PET allowed them to observe connectivity and glucose metabolism in the same study, alongside participants’ symptom reports.

That combination may help researchers develop questions for larger trials: whether changes in these brain measures are repeatable, whether they track meaningful changes in everyday function, and what dose or treatment schedule might matter. At present, the study’s small size and short follow-up mean the results should be treated as preliminary evidence about brain activity, not proof that NAC changes the course of MS. The findings also do not establish that an over-the-counter supplement is interchangeable with the trial’s combined intravenous and oral regimen.

Why Researchers Tested NAC in MS

Multiple sclerosis affects the central nervous system, and cognitive problems can occur alongside physical symptoms. In comments reported by MedPage Today, lead researcher Sahar Darabi Monadi said an estimated 40% to 70% of people with MS experience cognitive impairment, attributing it to inflammation and oxidative stress. Those figures and the explanation were presented by the researcher; they are not outcomes measured in this 36-person trial.

The research team’s rationale was that NAC may raise glutathione and reduce oxidative stress. Monadi said earlier studies had examined NAC in relation to glucose metabolism and fatigue in MS, while the current work assessed imaging measures of connectivity and metabolism together. Co-author Andrew Newberg also cited research involving NAC in Parkinson’s disease and chronic mild traumatic brain injury. Those studies concern other conditions and do not establish benefits for MS.

The trial’s delivery method was selected partly because the researchers were concerned that oral NAC absorption can vary, according to Newberg. That makes the study regimen different from simply taking an oral supplement: participants received both intravenous and oral NAC, alongside standard care. The report does not give enough information to assess how the results might apply to other formulations or dosing patterns.

“We hope it opens an opportunity to explore the use of NAC in a more detailed way, clarifying appropriate dosing regimens and duration as well as timing.”

— Andrew Newberg, MD, Thomas Jefferson University, as quoted by MedPage Today

Limits of the Four-Month Trial

The trial included only 36 participants, and the reported follow-up was about four months. The available report does not establish whether the imaging differences or symptom-score changes persist, affect daily functioning, or alter disability or disease progression. It also does not give effect sizes, detailed participant characteristics, or a full account of adverse events, so the magnitude and safety profile cannot be judged from the supplied findings.

It remains unclear how much of the reported symptom change reflects NAC rather than other factors, and whether results would hold in a larger group or with oral NAC alone. The researchers reported improvements in the treatment group, but those results do not amount to a recommendation to start NAC. People considering supplements or changes to MS care should discuss decisions with a qualified clinician.

Larger Studies Needed to Test NAC

The researchers said they want further work to clarify dose, treatment duration, and timing. A larger, longer study would be needed to test whether the imaging patterns can be reproduced and whether they correspond to sustained, clinically meaningful changes. It could also assess safety and compare the combined infusion-and-pill regimen with other approaches.

For now, the reported findings add an early research signal about NAC and brain imaging in MS. No next trial or timetable was specified in the source material, and it is not clear whether the researchers plan to test NAC as an add-on treatment in a larger clinical study.

Key Questions

What did the MS study find?

In a 36-person randomized trial, the group receiving NAC plus standard care showed changes in brain connectivity and glucose metabolism on imaging. Participants in that group also reported improvements in pain, fatigue, cognition, and attention over about four months.

Does this study prove NAC treats multiple sclerosis?

No. The study was small and short, and its results do not show that NAC slows MS progression or establishes it as an effective treatment. The findings are preliminary and need testing in larger studies.

How did participants receive NAC?

The treatment group received 50 mg/kg intravenously once a week and 500 mg orally twice daily on the other six days each week, in addition to standard care. The trial did not test oral NAC alone.

What remains unknown about the results?

The report does not establish whether the changes last, how large or practically meaningful the symptom improvements were, or whether NAC affects disability or disease progression. The available information also does not fully describe adverse events or show whether the findings apply to other doses and formulations.

Source: rss