Glucosamine May Contribute to Alzheimer’s Disease
/By Pat Anson
An over-the-counter supplement used by millions of people around the world to relieve joint pain has been associated with Alzheimer’s disease and other advanced forms of dementia, according to a new study.
Neuroscientists at the University of Florida say glucosamine raises the risk of someone progressing from mild cognitive impairment to Alzheimer’s disease by about 25 percent.
Glucosamine is an amino sugar found in shellfish that helps build cartilage, ligaments, tendons, and synovial fluid in joints. It is used annually by about 40 million Americans, many of them elderly, to reduce inflammation and symptoms of osteoarthritis.
What many seniors don’t realize is that glucosamine may also be accelerating the formation of protein plaques in their brain, which have been linked to dementia.
“A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse,” senior author Ramon Sun, PhD, a biochemist and molecular biologist, said in a press release.
It’s important to note that the study findings, published in the journal Nature Metabolism, are preliminary and don’t establish a cause and effect relationship between glucosamine and Alzheimer’s – only an association.
The findings are based on a large retrospective analysis of health records for over 50,000 patients diagnosed with Alzheimer’s disease-related dementias (ADRDs) or mild cognitive impairment (MCI). While most patients with MCI remained stable or even recovered cognitive ability, about 5% progressed to ADRD, representing a clinical worsening of cognitive decline.
About 8% of the patients studied reported taking glucosamine supplements. When compared to patients who didn’t take glucosamine, researchers saw a 25% higher risk of patients with MCI transitioning to ADRD in the glucosamine user group. In addition, glucosamine use was associated with a 25% increase in mortality risk among ADRD patients.
Researchers believe glucosamine crosses the blood-brain barrier and feeds into pathways that build sugar residue on protein cells. Patients with Alzheimer’s appear to be more vulnerable to this metabolic activity than those with healthy brains.
“The electronic health record data are very provocative,” said co-author Matt Gentry, PhD, chair of UF’s Department of Biochemistry and Molecular Biology. “While it’s an association and not proof of causality, it does raise an important clinical question that now deserves much more attention.”
In tests on genetically modified mice, the UF research team found that glucosamine significantly increased sugar residue on proteins in the brain and reduced the social recognition behavior of mice. When researchers chemically suppressed this process, their “social memory” improved.
Advanced imaging studies on human Alzheimer’s brains also showed significantly increased sugar attachment to proteins compared to healthy brains.
Taken together, the findings suggest that metabolic dysfunction is not simply a secondary aspect of Alzheimer’s pathology, but a contributing cause.
“Proteins are the cell’s molecular machines, and many of them need sugar tags added in just the right way to fold correctly, travel to the right place and do their jobs,” Gentry said. “What we found in Alzheimer’s is that this sugar-tagging system appears to be overactive. The Alzheimer’s brain is adding too many of these sugar structures, and this seems to contribute to the disease rather than protect against it.”
The good news about this research is that it could lead to new ways to prevent Alzheimer’s or slow its development.
“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.
Glucosamine is the fourth most widely used supplement in the United States. It is also widely used in China and Europe. Glucosamine is often combined with chondroitin to help build or restore joint cartilage.
While further studies are needed, the Mayo Clinic says glucosamine “might provide some pain relief” for people with knee osteoarthritis.
