Researchers conducted a cohort study that suggests oral N-acetylglucosamine treatment can hinder neurodegeneration and inflammation associated with multiple sclerosis (MS).
No matter an individual’s type of MS, all stages of the disease exhibit forms of neurodegeneration. The progression of neurological disability has been largely attributed to lasting brain inflammation and limited remyelination by the oligodendrocytes. In the management of MS, it has become clear that addressing the inflammation alone will not promote neurological repair and that “agents that directly stimulate myelin repair are needed.”
GlcNAc is a supplement that has a variety of uses due to its ability to modulate inflammation, neurodegeneration, and myelination. It has strong associations with the production of Asn (N)-linked glycans, which, as they branch out, regulate some of the integral mechanisms in MS pathogenicity, including microglia, myelination, hyperactive T cells, B-cell functioning, and neurodegeneration. To further assess the safety and biological influences of GlcNAc, researchers conducted a clinical trial to observe the impact of GlcNAc dosage on individuals with MS.
Participants were identified from a University of California, Irvine (UCI), patient pool, as well as non-UCI patients with MS who came across the study opportunity, between March 2016 and December 2019. Those included were split into 2 groups: taking 2 g of GlcNAc 3 times daily (6-g group) and taking 4 g 3 times daily (12-g group) over 4 weeks. The participants had blood drawn and clinical labs performed throughout a 3-week pretreatment period, as well their 4-week treatment and 4-week posttreatment period. Any adverse effects (AEs) were recording across all timeframes and an Expanded Disability Status Scale (EDSS, a 10-point assessment where lower scores indicate less severe disease states).
Serum GlcNAc levels were tracked and recorded as HexNAc (N-acetylhexosamine) in the results. Additionally, N-glycan branching was measured using the plant lectin Phaseolus Vulgaris leucoagglutinin (L-PHA).
The 6-g group consisted of 18 individuals and the 12-g group numbered 16. Baseline serum levels of pro and anti-inflammatory cytokines did not differ between the cohorts. Limited and mild gastrointestinal AEs were only reported by the 12-g group throughout the study period.
Oral treatment with GlcNAc and serum HexNAc increases correlated with dosing. Participants of the 6-g group experienced a 65% increase of serum levels and those of the 12-g group experienced a 112% increase. Similarly, L-PHA binding increased by an average of approximately 3% in the 6-g group and 7% in the 12-g group (P = .038 and .0065, respectively). The 6-g group did not exhibit significantly reduced serum levels of proinflammatory cytokines (interferon-γ, interleukin [IL]-6 and IL-17); however, reductions were observed in the 12-g group. The anti-inflammatory cytokine IL-10 paralleled this reduction, which was observed in the 12-g group but not 6-g group.
The authors noted that over the course of their trial, “serum neurofilament light chain (sNfL) emerged as a sensitive biomarker of acute neuroinflammation, therapy response, and predictor of long-term (> 15 years) disability worsening.” Upon cell injury, NfL is released and higher levels of NfL indicate more active, occurring neuro-axonal injury. During GlcNAc treatment, the 12-g cohort demonstrated significantly reduced levels of NfL (12.5% on average). No significant reduction was observed in the 6-g cohort, although this group was reportedly trending in a positive direction.
Additionally, both cohorts had significant reductions in their EDSS scores, with approximately 30% having improvements after 4 weeks of treatment.
Overall, oral GlcNAc treatment was shown to be safe and effective for managing inflammation and immune responses, and presented little AEs in patients. The researchers believe that these findings and their focus on N-glycan branching may provide insights for the clinical approach of other inflammatory and demyelinating disorders, as well as some autoimmune diseases. They conclude by positing that “GlcNAc therapy should additionally be considered for investigation in neurodegenerative disorders with microglia-associated inflammation, such as Alzheimer’s and Parkinson’s diseases.”
Sy M, Newton BL, Pawling J, et al. N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial. J Neuroinflammation. 2023;20(1):209. doi:10.1186/s12974-023-02893-9