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. 

Study Links Gabapentin to Increased Dementia Risk

By Crystal Lindell

Gabapentin (Neurontin) may significantly increase the risk of dementia and cognitive impairment, even for middle-aged patients who only took the nerve medication for six months.

That’s according to a new study, published in the Regional Anesthesia & Pain Medicine journal, which looked at health records for over 26,000 U.S. patients with chronic low back pain.

Researchers found that patients with six months or more of gabapentin use had a 29% higher risk of developing dementia and an 85% higher risk of developing mild cognitive impairment (MCI). 

Gabapentin was originally developed to prevent epileptic seizures, but is now commonly prescribed off-label as an alternative to opioids for pain management.

Researchers have long been concerned about gabapentin’s effects on neurotransmitters in the brain, while patients have complained the drug causes brain fog, dizziness, weight gain and worsens mood. 

Perhaps the most startling aspect of the study is that gabapentin increases the risk of dementia and cognitive decline in middle aged adults.

Dementia risk more than doubled and MCI risk tripled among 35–49 year olds. A similar pattern was observed among 50–64 year olds.

Risks also rose the more often patients use gabapentin. Those with 12 or more prescriptions were 40% more likely to develop dementia and 65% more likely to develop MCI than those with fewer prescriptions.. 

“Our findings indicate an association between gabapentin prescription and dementia or cognitive impairment within 10 years. Moreover, increased gabapentin prescription frequency correlated with dementia incidence,” wrote lead author Nafis Eghrari, a medical student at Case Western Reserve University School of Medicine.

“Our results support the need for close monitoring of adult patients prescribed gabapentin to assess for potential cognitive decline.”

As a patient who has taken gabapentin for chronic pain, these results are alarming to say the least. And I wonder if the findings would also apply to pregabalin (Lyrica) and other gabapentinoids in the same class of medications. I have also been prescribed Lyrica. 

I don’t believe I was ever warned that gabapentin could increase my risk of cognitive decline, despite the fact that was a known concern. I don’t know if such a warning would have deterred me from taking it, but that’s still a choice that should have been given to me. 

I am also concerned that the information about these very real risks associated with even relatively short-term gabapentin use will reach patients and prescribers. Sales of gabapentin and pregabalin have tripled from a decade ago, when they were first touted as safer alternatives to opioids. 

Gabapentin is FDA-approved for epilepsy and neuropathic pain caused by shingles, but is also prescribed off-label for depression, ADHD, migraine, fibromyalgia, bipolar disorder and postoperative pain.  

Anyone prescribed gabapentin for pain should be told that using the medication for just six months greatly increases their risk of developing dementia. However, I doubt that will happen. In my experience, while medical professionals are quick to point out the supposed risk of opioids like hydrocodone, they often push alternatives like gabapentin onto patients without much discussion. 

The assumption is always that anything must be safer than opioids. Unfortunately, that doesn’t always seem to be the case.