Common joint supplement linked to faster dementia progression

Clinical Takeaway: Clinicians caring for patients with mild cognitive impairment or dementia should consider asking about glucosamine use, which is often overlooked because it's available over the counter. While causality hasn't been established, these findings raise concerns about glucosamine supplementation in patients with established neurodegenerative disease and warrant discussion during medication reconciliation.

Glucosamine is widely used for osteoarthritis and joint pain and is often perceived as a benign supplement. Little is known, however, about its effects on neurodegenerative disease, despite its ability to cross the blood-brain barrier and participate in metabolic pathways involved in protein glycosylation.

In a new study integrating human brain tissue analysis, animal models, and electronic health record data, researchers identified excessive protein glycosylation ("hyperglycosylation") as a potential driver of Alzheimer's disease progression. The data suggest that glucosamine may exacerbate this pathway.

Because glucosamine use is common among older adults, the findings may have immediate relevance for clinicians caring for patients with cognitive impairment. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse,” said senior author Ramon Sun, PhD, director of the Center for Advanced Spatial Biomolecule Research at the University of Florida.

Among more than 41,000 patients with mild cognitive impairment, glucosamine use was associated with a 25% higher likelihood of progression to Alzheimer's disease–related dementia. In a separate cohort of more than 24,000 patients with established dementia, glucosamine use was associated with a 25% increase in mortality risk. Approximately 8% of patients in both cohorts had documented glucosamine use.

Evidence from human brain tissue and animal models supported the clinical observations. Brain tissue from patients with Alzheimer's disease showed markedly increased glycosylation compared with controls, and glucosamine supplementation worsened memory deficits in multiple mouse models of Alzheimer's disease. In contrast, interventions that reduced glycosylation improved cognitive performance in animals.

The association appeared to be specific to established neurodegenerative disease. Glucosamine didn't worsen cognitive outcomes in cognitively normal mice and wasn't associated with increased mortality among patients with mild cognitive impairment.

The human findings were observational, and the study cannot establish causality. The authors emphasized that a prospective randomized clinical trial is needed before changes to clinical recommendations can be made. Still, the results highlight a potentially modifiable exposure in a population with few disease-modifying treatment options.

“Overall, these results establish hyperglycosylation as a pathological driver of Alzheimer's disease and highlight glycan metabolism as an actionable target in the fight against Alzheimer's disease,” the study authors concluded.

Source: Hawkinson TR, et al. 2026 June 9. Nat Metab. Hyperglycosylation is a metabolic driver of Alzheimer's disease