People with Alzheimer’s disease who took the common supplement glucosamine were 25% more likely to die within five years than those who didn’t. That’s the key finding of a new study that my colleagues and I published in the journal Nature Metabolism.
Glucosamine is a sugar molecule that’s sold over the counter as a remedy for joint pain and arthritis. More than 40 million Americans take it each year.
We found that glucosamine also affected people in the earliest stage of memory loss, a condition called mild cognitive impairment. People in this early stage of dementia who were taking glucosamine were 25% more likely to progress to full Alzheimer’s.
Our analysis of patients with Alzheimer’s disease was based on anonymized medical records from the University of Florida Health system. We included 24,000 patients with dementia and 41,000 with mild cognitive impairment, comparing people who took glucosamine with those who didn’t.
We then conducted experiments in mice engineered to have Alzheimer’s-like symptoms to identify the potential mechanism behind how glucosamine may affect the brain. We found that blocking the enzyme that makes sugars like glucosamine improved dementia symptoms in mice. In contrast, feeding those same mice glucosamine made memory loss worse. Healthy mice given the same supplement showed no effect.
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.
