Glucosamine is a go-to supplement for millions of older adults hoping to ease their aches and pains of arthritis. Available without a prescription and often marketed as a natural way to support joint health, it has generally enjoyed a reputation for safety. Now a new study suggests there may be reason for caution among people experiencing memory problems when using glucosamine.

Researchers at the University of Florida found that glucosamine use was associated with a greater likelihood that people with mild cognitive impairment (MCI) would progress to Alzheimer's disease.

Mild cognitive impairment is often considered an intermediate stage between normal age-related memory changes and dementia. Not everyone with MCI develops Alzheimer's disease, but many do.

Because glucosamine is sold over the counter, millions of older adults take it without discussing it with their physicians.

To investigate whether glucosamine might play a role, researchers examined de-identified electronic records from the University of Florida Health system between 2012 and 2024. The team analyzed records from approximately 24,000 patients with Alzheimer's disease and related dementias and more than 41,000 patients with mild cognitive impairment. About 8 percent of this group reported taking glucosamine supplements.

After accounting for factors such as age, sex and demographics, the researchers, led by Ramon Sun, Ph.D., director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation at the University of Florida's McKnight Brain Institute, along with collaborators Yi Guo, Ph.D. and Jiang Bian, Ph.D., noted that people with MCI who took glucosamine had a 25 percent higher likelihood of progressing to dementia than those who did not use the supplement.

They also reported that among people already diagnosed with Alzheimer's disease and related dementias, glucosamine use was associated with a 25 percent higher risk of death during the study period.

To be clear, the findings do not prove that glucosamine caused dementia to worsen. Because this was an observational study based on medical records, it can only identify an association, not a direct cause-and-effect relationship. Still, the researchers wanted to understand why such a link might exist.

To do that, they turned to laboratory studies using genetically modified mice that develop Alzheimer's-like symptoms and found that glucosamine appeared to increase a process known as hyperglycosylation, in which excess sugar molecules attach to proteins in the brain. When this process intensified, memory problems worsened. When researchers blocked the pathway, memory improved. Similar abnormalities were also found in brain tissue from people who had Alzheimer's disease.

The apparent risk was observed in people who already had cognitive impairment. The findings do not suggest that glucosamine causes Alzheimer's disease in cognitively healthy adults.

The findings add to growing evidence that disruptions in metabolism may contribute to neurodegenerative disease. “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 plagues and tangles,” said Sun said, in a press release.

The results should be viewed as an important warning sign rather than definitive proof, according to the study's co-author Matt Gentry, Ph.D., chair of the University of Florida Department of Biochemistry and Molecular Biology. “The electronic health record data are provocative,” he said. “While it's an association, not proof of causality, it does raise an important clinical question that now deserves more attention.”

The researchers also noted an important distinction: the apparent risk was observed in people who already had cognitive impairment. Their findings do not suggest that glucosamine causes Alzheimer's disease in cognitively healthy adults. In fact, some earlier studies reported lower dementia risk among healthy people who take the supplement.

Because glucosamine is sold over the counter, millions of older adults take it without discussing it with their physicians. The new findings suggest that people diagnosed with mild cognitive impairment or Alzheimer's disease may want to have that conversation.

Much more research is needed, including studies that follow patients after they stop taking glucosamine. For now, experts say the findings should not cause panic, but they do provide another reminder that even widely used supplements can have unexpected effects, particularly in vulnerable brains.

Researchers are continuing to investigate the connection, but the message is already worth noting. “Natural” does not always mean risk-free, particularly for people with cognitive impairment.

The study is published in Nature Metabolism.