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. 

Chronic Pain Causes Brains to Age More Rapidly

By Pat Anson, PNN Editor

Poorly treated or untreated chronic pain can lead to a number of other health problems, from high blood pressure and insomnia to depression and anxiety.

Now there is evidence that chronic pain also causes brains to age more rapidly, raising the risk of developing Alzheimer’s disease and other neurological problems associated with aging.

“Our findings highlight the need to address chronic pain, not just in older individuals but in potentially everyone, as pain may have unintended consequences in the brain that we don’t yet fully understand,” said lead author Yenisel Cruz-Almeida, PhD, a researcher at the University of Florida Institute on Aging.

Over a three-year period, Cruz-Almeida and her colleagues used magnetic resonance imaging (MRI) to measure the volume of gray and white matter in the brains of 47 older adults, ages 60 to 83.  The volunteers were free of neurological disorders and in generally good health, although 33 of them had some type of chronic pain.

Volunteers who did not have chronic pain had brains that appeared four years younger than their actual age.

Chronic pain sufferers had brains that appeared an average of two years older. They were also more likely to have greater pain intensity, have a “less agreeable personality” and be less emotionally stable, according to researchers.

The University of Florida produced this video on the study, which was recently published online in the journal Pain.

“Not everybody ages the same way,” said Cruz-Almeida. “I don’t want people to think, ‘Oh, I have chronic pain. I’m doomed.’ This is not the case. That is not the message we want to get out. There is more nuance than that.”

Interestingly, the volunteers who reported getting pain treatment in the last three months had younger-appearing brains compared to those that did not, suggesting that pain relief slows brain aging. Pain sufferers who had a happier outlook on life and were generally more upbeat also had younger-appearing brains.

“The pain experience is not just in your brain,” said Cruz-Almeida. “There appear to be avenues or things that could be done to change brain age.

“Our findings also suggest that both pain treatments and psychological traits may significantly mitigate the effect of pain on the aging brain and could further decrease the risk of age-related deterioration and death.”

Cruz-Almeida is planning additional research with a larger sample of older adults that will look at ways to alleviate accelerated brain aging.