Does Glucosamine Usage Make You More Likely to Die or Develop Dementia?

A recent article[i] was published concluding that glucosamine use was “linked” to worsening dementia. Our team has reviewed this article and have many rebuttals for the arguments made.

This was a study on 5xFAD mice that were used as a model for Alzheimer’s dementia in humans. 5xFAD mice are transgenic (mutant) mice that feature five mutations that cause them to develop familial Alzheimer's. Even without intervention, these mice would go on to develop Alzheimer’s. They fed these mutant mice and normal wildtype mice physiological dose of glucosamine and compared how it affected their development of Alzhemer’s dementia. The dosage in the trial was 457 mg /kg per day, with the dose calculated based on human therapeutic equivalent dose of ~2,500 mg/day or 36 mg/kg per day.

The authors of the study found that glucosamine supplementation did not result in brain hyperglycosylation of wildtype (normal) mice in contrast to the robust increase observed in 5xFAD mice. They found that hyperglycosylation of proteins (adding sugars to proteins) in the brain is concerning and is perhaps the main driver in Alzheimer’s dementia.

However, it is important not to extrapolate the results of this study on mutant mice that have inherent impairments in glucosamine metabolism and the implications for this study should not be extrapolated to healthy humans.

The second part of this study analyzed the medical records of patients at the University of Florida medical system. They looked at elderly populations who told their doctors they were taking a glucosamine supplement and found a 25% increase in mortality risk among Alzheimer's disease and related dementia (ADRD) patients who were also using glucosamine compared to those that weren't.

Glucosamine is commonly used by people with arthritis who have impaired mobility. Taking glucosamine implies that these patients may have osteoarthritis (OA) or other forms of arthritis such as rheumatoid arthritis. A meta-study, or study featuring data from other studies, found that OA is associated with a 21% increase in mortality from cardiovascular disease[ii]. This association lines up with the 25% increase found in the recent study.

The recent study also looked at patients had mild cognitive impairment (MCI) and were using glucosamine compared those patients who had MCI and did not take glucosamine. They found that those with MCI and were using glucosamine were 25% more likely to progress to ADRD than their counterparts not taking glucosamine.

Again, this study fails to account for the meaning of glucosamine usage. Those taking glucosamine are likely to have some form of arthritis. Mobility is of utmost importance for metabolism and blood sugar control. Another meta-study found that people with OA are already 20-36% more likely to develop dementia than their healthy counterparts[iii].

OA is also associated with diabetes mellitus (DM). Another meta-study found that having OA was associated with a 41% increase in associated DM diagnoses[iv]. DM is caused by impaired sugar (glucose) metabolism that leads to elevated blood sugar levels. These elevations in blood sugar can lead to hyperglycosylation of proteins in the brain that drive dementia.

In conclusion, this means that those with osteoarthritis and who are using glucosamine may be dealing with multiple issues that are increasing their mortality and risks of other diseases. It does not mean that using glucosamine makes you more likely to die or likely to develop dementia.

About the Author:

Dr. Bryan Do, D.O.

Dr. Do co-founded DrFormulas in 2010 with his wife and partner. They completed medical school together. Their experience with the healthcare system and common medical problems has given them insight into the human body and most common medical problems. In addressing these problems, they take an integrative and holistic approach that is not bound by traditional medicine. Their focus is immunology, diet, and exercise and their goal is to maximize your health and well-being using all the tools and resources available to you.