Recent research published in Nature Metabolism reveals a concerning link between the supplement glucosamine and increased mortality in those with Alzheimer’s disease. The study, conducted by my team and me, shows that individuals with Alzheimer’s who consumed glucosamine had a 25% higher chance of dying within five years compared to non-users.
Glucosamine, commonly marketed as an over-the-counter treatment for joint pain and arthritis, boasts a user base of over 40 million Americans annually. Despite its popularity, these findings suggest potential risks for certain individuals.
Moreover, our study indicates that glucosamine may also negatively impact individuals with mild cognitive impairment, an early stage of dementia. Those in this group who took the supplement were 25% more likely to advance to full-blown Alzheimer’s disease.
Our research relied on anonymized medical data from the University of Florida Health system. We scrutinized records of 24,000 dementia patients and 41,000 individuals with mild cognitive impairment, comparing outcomes between those who used glucosamine and those who did not.
To delve deeper into these effects, we experimented with mice genetically modified to exhibit Alzheimer’s-like symptoms. Our findings revealed that inhibiting the enzyme responsible for producing sugars like glucosamine alleviated dementia symptoms in these mice. Conversely, administering glucosamine exacerbated memory loss, while healthy mice showed no significant response to the supplement.
Why it matters
The Food and Drug Administration classifies glucosamine as a dietary supplement, not a prescription drug. As a result, anyone can buy it over the counter without seeing a doctor.
Glucosamine is an amino sugar. Composed of glucose and an amino acid called glutamine, these molecules are used by the body to build new cells. Because glucosamine is not considered an essential nutrient, glucosamine deficiency is not a recognized condition. However, people take the supplement based on anecdotal reports that it improves joint health, especially in the knees.
For more than a decade, my team and I at the University of Florida have studied how the brain uses and processes sugar and what goes wrong with that chemistry in people who have Alzheimer’s disease.
A lesser-known problem associated with Alzheimer’s disease is that brain cells and proteins build up extra sugar coatings. Brain cells and proteins normally carry short chains of sugar on their surface called N-glycans. These sugars guide a newly made protein into its three-dimensional shape and help it attach to other proteins it works with.
But in people with Alzheimer’s disease, the chains pile up where they don’t belong. The proteins underneath them start to fail, leading to memory loss and cell death. This condition is called hyperglycosylation.
Given that about 7.2 million Americans ages 65 and older live with Alzheimer’s disease, we estimated that many were also taking glucosamine for joint health. We hypothesized that this sugar amine may be contributing to cognitive decline.
Earlier studies have linked glucosamine supplements to a lower dementia risk in cognitively healthy adults. Our findings do not contradict those reports but qualify them. While glucosamine appears safe and potentially protective for a healthy brain, it may be harmful for a brain that is already experiencing cognitive decline.
What still isn’t known
Since our study was based on patient records rather than a controlled experiment in people, it cannot show that glucosamine causes faster cognitive decline – only that there’s an association.
Answering this question would require a study that randomly administers glucosamine to some patients and not to others. But if glucosamine may increase the risk of dementia, giving patients glucosamine would be unethical.
In addition, we do not yet know whether the apparent harm glucosamine has on the brains of people with memory problems depends on the dose, the brand of the supplement, or on how long people take it. We also do not know whether this finding applies to other forms of dementia.
What’s next
One way to test whether glucosamine directly causes cognitive decline would be a clinical trial on patients who took glucosamine and then discontinued it. About 8% of dementia patients in our database fall into that category. We hope to follow them for several years to see whether stopping the supplement slows their cognitive decline.
We are also screening compounds that block the N-glycan molecule and reduces the buildup of sugars on brain cells to see whether this might slow or reverse Alzheimer’s disease.
Finally, we plan to explore whether other supplements that the body breaks down in similar ways to glucosamine carry comparable risks for brains experiencing cognitive decline.