Glucosamine and Alzheimer’s: Why Scientists Are Asking Questions About a Popular Joint Supplement

Glucosamine is one of the most popular over-the-counter supplements for achy joints, especially among older adults. A new study from the University of Florida now suggests it deserves a closer look in people who already have memory and thinking problems. The researchers stress that the results are preliminary and do not show that the supplement causes harm.

What the researchers found in patient records

The team, led by senior author Ramon Sun, used artificial intelligence to analyze deidentified UF Health records from 2012 to 2024. They focused on patients diagnosed with Alzheimer’s disease or a related dementia (ADRD) and on patients with mild cognitive impairment (MCI), a stage where memory or thinking problems are greater than expected for a person’s age but don’t necessarily disrupt daily life.

In both groups, about 8% of patients reported taking glucosamine. That amounted to 1,896 people with ADRD and 2,750 people with MCI. After adjusting for age, sex and demographics, two patterns stood out:

·         Among people with MCI, glucosamine use was associated with a 25% higher likelihood of progressing to dementia.

·         Among people who already had ADRD, glucosamine use was associated with a 25% higher risk of death over a defined period. This was not seen in the MCI group, which hints that any effect may be stronger once dementia is established.

This kind of analysis can only show associations. People who take a supplement may differ from those who don’t in ways the study couldn’t fully account for, so the records alone cannot show that glucosamine speeds up disease.

A possible mechanism: too many sugar tags

The researchers also looked for a biological explanation. Cells routinely attach sugar structures to proteins, a process that helps proteins fold correctly, reach the right location and do their jobs. The team found signs that this sugar-tagging system is overactive in Alzheimer’s disease. The study’s title calls the problem hyperglycosylation and describes it as a metabolic driver of the disease.

Glucosamine is a sugar-related molecule that can cross the blood-brain barrier and feed into the pathways that build these sugar structures. Supplements can be made from shellfish shells or corn. The researchers suggest that the same molecule may act differently in a healthy brain than in one affected by Alzheimer’s, and that the Alzheimer’s brain may be especially vulnerable to this pathway.

Evidence from mice and human brain tissue

To test the idea, the team turned to genetically modified mice that model Alzheimer’s disease. Glucosamine markedly increased the attachment of sugars to proteins inside cells, and the treated mice performed worse on a test of social memory, the ability to recognize other animals. When the researchers used a chemical treatment to suppress the sugar attachment, memory performance improved. That suggests excessive sugar tagging may play a direct role in the memory problems rather than just appearing alongside them.

Human brain tissue told a similar story. Samples from people with Alzheimer’s disease, provided by the UF Neuromedicine Brain and Tissue Bank, showed significantly more sugar attachment than tissue from people without the disease. A spatial technology developed in Sun’s lab, which can map thousands of molecules in tissue, helped reveal these metabolic changes.

Beyond plaques and tangles

Much Alzheimer’s research has focused on amyloid plaques between brain cells and tau tangles inside neurons. This work adds to a growing body of evidence that disrupted metabolism may also drive the disease. Sun suggests that correcting the metabolic defect could complement treatments aimed at plaques and tangles, and that the overactive sugar-tagging pathway could become a drug target in its own right.

What this does and doesn’t mean

The study raises an important clinical question, but it does not establish that people should stop taking glucosamine. A controlled human clinical trial will be needed to determine whether the supplement directly accelerates Alzheimer’s progression and, if so, which patients are most at risk. In the meantime, anyone with memory concerns who takes glucosamine may want to talk with their doctor about it rather than making changes on their own.

Sources

Press release: UF Health, via ScienceDaily

Original paper: Hawkinson TR, et al. Hyperglycosylation is a metabolic driver of Alzheimer’s disease. Nature Metabolism, 2026; 8(6): 1410. https://doi.org/10.1038/s42255-026-01538-4 

Source: Glucosamine and Alzheimer’s: Why Scientists Are Asking Questions About a Popular Joint Supplement