Millions of people around the world take glucosamine, an over-the-counter dietary supplement commonly used to ease joint pain. Now, a new study published in the scientific journal Nature Metabolism raises a troubling possibility: use of the supplement may be linked to faster progression of Alzheimer’s disease and worsening outcomes among patients already diagnosed with dementia.
The study, conducted by researchers from the University of Florida and other U.S. institutions, found that among people with mild cognitive impairment, known as MCI and often considered a possible early stage before dementia, glucosamine use was associated with a 25% higher risk of progression to dementia. Among patients who already had dementia, the supplement was linked to a 25% higher risk of death during the follow-up period.
The findings were published alongside an analysis of medical records collected between 2012 and 2024 from the University of Florida health system, which included tens of thousands of patients with varying degrees of cognitive decline.
The process that may worsen Alzheimer’s
Glucosamine is a substance found naturally in the body and plays an important role in building cartilage in the joints. Millions of people take it as a dietary supplement to ease joint pain and symptoms of osteoarthritis. Despite its popularity, scientists remain divided over how effective it is, and studies over the years have produced mixed findings on whether it reduces pain or improves function.
Alzheimer’s disease is a degenerative brain disease marked by a gradual decline in memory and cognitive abilities. Despite decades of research, the precise mechanisms that drive its progression are still not fully understood.
In the new study, researchers focused on a biological process called glycosylation, in which sugar molecules attach to proteins. It is a normal and essential cellular process, but the researchers found that in the brains of Alzheimer’s patients, it appears to occur at unusually high levels, a state they described as hyperglycosylation.
By combining metabolic tests, analysis of human brain tissue after death and mouse models of Alzheimer’s disease, the researchers found that glycosylation levels in the brain rise as the disease progresses. According to the study, the process appears to stem from increased production of sugar molecules involved in building glycans, rather than from slower breakdown.
“Alzheimer’s disease is a devastating neurodegenerative disease characterized by progressive cognitive decline,” the researchers wrote. “Our findings indicate that hyperglycosylation is an active driver of disease development, not merely a byproduct.”
Memory damage in mice
To examine whether there could be a causal link between glucosamine and the process they identified in the brain, the researchers gave glucosamine to mice with Alzheimer’s at a dose calculated to be equivalent to a common therapeutic dose in humans. After just two weeks, glycosylation levels in the mice’s brains increased. The mice also performed worse on tests of memory and social behavior.
By contrast, when the researchers experimentally reduced activity in the glycosylation pathway in the brain, glycosylation levels fell and the mice’s cognitive performance improved. According to the researchers, these findings strengthen the possibility that increased glycosylation itself contributes to cognitive impairment.
The link found in humans
To examine whether the findings seen in mice might also be relevant to humans, the researchers analyzed a large database of medical records from the University of Florida health system. They identified 24,481 patients with dementia and 41,884 patients with mild cognitive impairment. In both groups, about 8% of patients were documented as regular glucosamine users.
The analysis found that among people with mild cognitive impairment, glucosamine users had a 25% higher risk of progressing to dementia. Among patients already diagnosed with dementia, use of the supplement was linked to a 25% higher risk of death during the follow-up period. However, among people with mild cognitive impairment, glucosamine use was not linked to a higher risk of death.
Dr. Polina Spector, a neurologist and coordinator of the neurocognitive field at Carmel Medical Center, part of Clalit Health Services, stressed that the findings should be interpreted cautiously.
“At this stage, this is the first study of its kind to point to a possible link between glucosamine and worsening dementia,” she said. “The study was based mainly on experiments in laboratory mice. The part that examined the link between glucosamine use and dementia progression and mortality was based on a retrospective analysis of medical records, not on a study that directly followed Alzheimer’s patients who received glucosamine over time. Therefore, it does not allow us to determine a cause-and-effect relationship.”
Spector said other factors could explain the findings.
“For example, patients who take glucosamine may suffer from other underlying diseases, such as diabetes or additional medical conditions, which themselves may be linked to faster worsening of cognitive decline,” she said.
She also noted that other studies have produced a different picture.
“For example, a study published in 2023 in the journal BMC Medicine found a link between regular glucosamine use and a lower risk of developing dementia,” Spector said. “Therefore, at this stage there is no reason to panic or draw firm conclusions, and we should wait for additional studies that examine the issue more deeply.”
The researchers emphasize that the study is observational and based on medical records, meaning it cannot prove that glucosamine causes dementia or directly worsens it. Still, they argue that the combination of findings in human brain tissue, results from mouse experiments and clinical data justifies further research.
In an editorial published alongside the study, the findings were described as pointing to glycosylation as a biological pathway that could one day serve as a target for new Alzheimer’s treatments. The researchers called for a large, randomized, double-blind clinical trial to test whether glucosamine use affects the pace of cognitive decline in dementia patients.