A recent study revealed that individuals with Alzheimer’s disease who took glucosamine, a popular supplement often used for joint pain relief, had a 25% higher chance of passing away within five years compared to those who didn’t take it. This finding was published in the journal Nature Metabolism by a team of researchers including myself.
Glucosamine, a sugar molecule available over the counter, is used by over 40 million Americans annually as a remedy for arthritis.
Interestingly, our research also indicated that glucosamine impacted individuals experiencing mild cognitive impairment, which is an early stage of memory loss. Those taking glucosamine were 25% more likely to advance to full-blown Alzheimer’s.
Analyzing anonymized health records from the University of Florida Health system, we looked at 24,000 patients with dementia and 41,000 with mild cognitive impairment, contrasting those who used glucosamine with those who did not.
We conducted experiments on mice genetically modified to exhibit Alzheimer’s symptoms to uncover the possible mechanisms through which glucosamine may impact brain function. Our findings showed that inhibiting the enzyme responsible for producing sugars like glucosamine led to improvements in dementia symptoms in mice. Conversely, administering glucosamine made memory issues worse, while healthy mice didn’t show any negative effects.
Why it matters
The FDA classifies glucosamine as a dietary supplement, allowing anyone to purchase it without a doctor’s consultation.
This amino sugar, formed from glucose and the amino acid glutamine, is utilized by the body to generate new cells. Notably, glucosamine is not deemed an essential nutrient, and thus a deficiency isn’t recognized. However, many people take it based on anecdotes suggesting it enhances joint health, particularly in the knees.
Over the past decade, my team and I at the University of Florida have been investigating how the brain utilizes and processes sugar, especially what goes awry in individuals with Alzheimer’s.
One lesser-known challenge related to Alzheimer’s is the accumulation of excessive sugar coatings on brain cells and proteins. Typically, these cells carry short sugar chains known as N-glycans on their surfaces. These sugars help shape newly manufactured proteins and assist them in binding with other proteins.
However, in Alzheimer’s patients, these chains accumulate abnormally. This accumulation disrupts the underlying proteins, leading to memory loss and cell death, a condition referred to as hyperglycosylation.
Considering that approximately 7.2 million Americans aged 65 and older have Alzheimer’s, we speculated that many might also be using glucosamine for joint care. We suspected this sugar amine could be linked to cognitive decline.
Previous research has suggested that glucosamine might reduce dementia risk in cognitively healthy adults. Our findings don’t contradict these earlier studies but do add a nuance. While glucosamine seems safe and potentially beneficial for healthy brains, it might pose risks for those already facing cognitive issues.
What still isn’t known
Since our study relied on patient records rather than a controlled experiment among individuals, we can’t definitively claim that glucosamine accelerates cognitive decline—only that there’s a correlation.
To truly answer this, a controlled study would need to give some patients glucosamine while withholding it from others. However, if glucosamine indeed heightens dementia risk, administering it in such a trial would be ethically questionable.
We still lack clarity on whether the potential detriment of glucosamine for those experiencing memory issues relates to dosage, the brand, or the duration of use. Furthermore, it remains uncertain if these findings apply to other forms of dementia.
What’s next
One potential approach to determine if glucosamine causes cognitive decline would involve a clinical trial where patients who had been using glucosamine stop taking it. About 8% of dementia patients in our database fit this criterion. We hope to monitor them over the years to see if discontinuing the supplement halts cognitive decline.
Additionally, we are exploring compounds that can inhibit the N-glycan molecule to lessen the sugar buildup in brain cells, aiming to identify possible strategies for slowing or reversing Alzheimer’s disease.
Lastly, we intend to investigate whether other supplements that metabolize similarly to glucosamine may likewise introduce risks for individuals undergoing cognitive decline.
