Can a readily available supplement suppress inflammation in MS?

Study shows n-acetyl glucosamine (NAG) may help to inhibit disease
​progression.

Inflammation – it’s something we often talk about for its impact on the progression of many autoimmune diseases, including neuroimmune conditions like multiple sclerosis (MS). ​

And while we do have a wide variety of drug resources that address inflammation, these drugs do not restore myelin, the protective sheath that surrounds nerves. In order to stop MS from progressing, we desperately need treatments that can potentially support the repair of damaged myelin.
 
A 2023 study shows some very promising results with n-acetyl glucosamine or NAG (also referenced as GLcNAc), an accessible dietary supplement derived from the outer shells of shellfish; vegetarian/vegan forms (non-animal derived) are also available.
 
While NAG has regularly been included as part of a treatment protocol in conditions like osteoarthritis and inflammatory bowel disease, researchers were able to demonstrate its ability to help the brain as well!
 
The study, “N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial,” concluded that by suppressing damaging autoimmune responses, NAG may contribute to restoring neurological function in some MS patients.
 
Some of the science.
 
NAG is a triple modulator of inflammation, myelination, and neurodegeneration. In mice subjects, it crosses the blood-brain barrier (BBB). This results in an increase in N-glycan branching, suppression of inflammatory demyelination by T and B cells, and triggering stem/progenitor cell mediated myelin repair.
 
N-glycan branching independently regulates five critical pathogenic mechanisms in MS: T-cell hyperactivity; B cell innate function; microglia; myelination, and neurodegeneration.
 
(Note: if you keep these brief explanations below in italics, I see it as an image/graphic so it’s distinct from the content, just to clarify the terms above)
 
Good to know…
 
T-cell hyperactivity: when these white cells are overworked, we may become more susceptible to diseases of an overactive immune response.
 
B cell innate function: B cells, another white cell, protect us from infection through the production of antibodies.
 
Microglia: the resident immune cells of the brain, microglia act as regulators against pathogens.
 
Myelination: the formation of the protective sheath around nerves.
 
Neurodegeneration: the process whereby structures or functions of neurons or nerve cells are impaired, leading to neurodegenerative disease.
                                                             
The study design.
 
Methods comprised an open label, dose-escalation mechanistic trial of oral NAG at 6 g (n = 18) and 12 g (n = 16) for 4 weeks. The study was conducted in MS patients, who at the time were on glatiramer acetate and not in relapse, from March 2016 to December 2019. Researchers sought to assess any changes in serum NAG, lymphocyte N-glycosylation and inflammatory markers and clinical response via the Expanded Disability Status Scale or EDSS, a standardized test used in research settings to measure MS-related disease outcomes.
 
The findings.
 
Oral NAG dose-dependently reduced serum levels of the anti-inflammatory cytokine IL-10, which is increased in the brain of MS patients. Thirty percent of treated patients displayed confirmed improvement in neurological disability, with an average EDSS score decrease of 0.52 points. A reduction in neurofilament light chain (NfL) levels was also observed; neurofilament light chain (NfL) is a blood biomarker that can provide clinically useful information about prognosis and therapeutic efficacy in MS.
 
The benefits.
 
Researchers noted that in addition to its novel mechanism of action that targets both immune and neural stem cells, NAG has several advantages over some existing therapies. It’s generally affordable, historically safe, and well tolerated with few, if any, side effects (i.e., minimal and limited gastrointestinal discomfort). And as an over-the-counter dietary supplement, it’s also widely available.
 
Summing up…
 
As reported by the researchers, the findings from this study are certainly encouraging and warrant additional investigations to determine the full efficacy of NAG supplementation. The scientific team also concluded that the results and the focus on N-glycan branching may also be applicable in future exploratory trials of other neurodegenerative and autoimmune disorders with microglia-associated inflammation, such as Alzheimer’s and Parkinson’s.
 
As with any dietary supplement, our practice ALWAYS recommends choosing a high quality, third-party tested product; if desired, patients may purchase the same supplement used in the study here or at several online retailers.
 
Stay informed, stay curious, and stay on top of your own health plan - understanding your options is incredibly important to your wellbeing today and tomorrow. So please let us know how we can help or answer any of your questions. We are here for you!
 
In hope and healing,
Dr. Suzanne Gazda
 
References:
 
Sy, M., Newton, B.L., Pawling, J. et al. N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial. J Neuroinflammation 20, 209 (2023). https://doi.org/10.1186/s12974-023-02893-9
 
Mazzuli, J. Development of GlCNAc as disease modifing treatment for Parkinson’s Disease. Northwestern University. 2019. https://www.scholars.northwestern.edu/en/projects/development-of-glcnac-as-disease-modifying-treatment-for-parkinso-3
 
Paharia, P. The association between regular glucosamine use and risk of dementia. News Medical Life Sciences. 2023. https://www.news-medical.net/news/20230403/The-association-between-regular-glucosamine-use-and-risk-of-dementia.aspx
 
Lee, B.E., Suh, PG. & Kim, JI. O-GlcNAcylation in health and neurodegenerative diseases. Exp Mol Med 53, 1674–1682 (2021). https://doi.org/10.1038/s12276-021-00709-5
 
Brandt AU, Sy M, Bellmann-Strobl J, et al. Association of a Marker of N-Acetylglucosamine With Progressive Multiple Sclerosis and Neurodegeneration. JAMA Neurol. 2021;78(7):842–852. doi:10.1001/jamaneurol.2021.1116 https://jamanetwork.com/journals/jamaneurology/fullarticle/2779917
 
Starossom SC, Mascanfroni ID, Imitola J, Cao L, Raddassi K, Hernandez SF, et al. Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity. 2012;37(2):249–63.