Joint pain supplement taken by millions may speed up Alzheimer's disease progression, scientists warn

Glucosamine remains one of the most popular over-the-counter remedies for joint pain, particularly among older adults.

It is used annually by about 40 million Americans to reduce inflammation and symptoms of osteoarthritis.

In some of the largest health evaluations, such as the UK Biobank, approximately 19.5 per cent of participants report regular glucosamine use.

"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, director of the Center for Advanced Spatial Biomolecule Research.

The research team employed artificial intelligence to analyse anonymised UF Health records spanning 2012 to 2024, examining patients diagnosed with either Alzheimer's disease and related dementias or mild cognitive impairment.

Some eight per cent of both patient groups reported using glucosamine, comprising 1,896 individuals with established dementia and 2,750 with mild cognitive impairment.

After adjusting for age, sex and demographic factors, the data revealed a troubling pattern.

Among patients already living with dementia, glucosamine consumption was linked to a 25 per cent higher mortality risk.

Notably, this elevated death rate did not appear in the mild cognitive impairment cohort, suggesting the supplement's effects may prove more pronounced in those with advanced disease.

The researchers uncovered a potential mechanism behind these findings involving an overactive metabolic process in the brain.

Glucosamine, a naturally occurring sugar-related compound, can penetrate the blood-brain barrier and contribute to pathways that attach sugar structures to proteins.

"Our results suggest that altered metabolism is a significant contributor to Alzheimer's progression and, in addition, addressing the metabolic defect could be an important complement to approaches focused on Alzheimer's plaques and tangles," Sun said.

Matt Gentry, chair of UF's Department of Biochemistry and Molecular Biology, explained that brains affected by Alzheimer's appear to add excessive sugar tags to proteins.

"The electronic health record data are very provocative," Gentry said. "While it's an association and not proof of causality, it does raise an important clinical question that now deserves much more attention."

Experiments using genetically modified mice demonstrated that glucosamine significantly boosted sugar attachment to cellular proteins, with treated animals displaying worsened recognition memory deficits.

When scientists chemically blocked this attachment process, memory function improved.

Analysis of brain specimens from the UF Neuromedicine Brain and Tissue Bank revealed markedly elevated sugar attachment in Alzheimer's patients compared with healthy controls.

These combined findings indicate that metabolic dysfunction may actively drive disease progression rather than merely accompany it.

The researchers emphasised that their results remain preliminary and require validation through human clinical trials before any definitive conclusions can be drawn about glucosamine's safety for dementia patients.