On June 9, neuroscientists from the University of Florida (UF) said they found an association between taking glucosamine supplements and a higher likelihood of progressing from mild cognitive impairment to Alzheimer’s disease.

The study was published in Nature Metabolism and was based on a large analysis of patient records and supporting data from advanced imaging technology used to scan human brain specimens and Alzheimer’s disease mouse models.

The team used artificial intelligence (AI) to comb through deidentified UF health records from 2012-2024 for patients diagnosed with Alzheimer’s disease and related dementias (ADRD) or mild cognitive impairment (MCI). They found around 8 percent of both types of patients reported taking glucosamine—1,896 with ADRD and 2,750 with MCI.

Researchers said taking glucosamine was associated with a 25 percent increase in mortality risk, or the likelihood of death within a specific time frame, among ADRD patients. For the MCI group, there was no such impact, suggesting “the impact of glucosamine may be greater in patients with established dementia.”

“In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias, such as Lewy body or frontotemporal dementia,” said senior author Ramon Sun, PhD, associate professor, director of the Center for Advanced Spatial Biomolecule Research (CASBR), and associate director for innovation at UF’s McKnight Brain Institute. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.”

Dr. Jacob Teitelbaum, board certified internist, author and fibromyalgia/fatigue expert, said the study does not mean glucosamine caused the increased risk of dementia. Instead, it shows what has been demonstrated in numerous other studies—chronic pain is associated with a 43 percent higher risk of dementia.

“In my opinion, the conclusion of the study is unsound because patients with arthritis commonly exhibit cognitive decline over time. It is far more likely that the chronic arthritis pain caused the increased dementia, not the glucosamine,” Dr. Teitelbaum explained.

He added at least three previous reports show no or negative associations between glucosamine use and dementia, with one suggesting cognitive benefits. Large-scale epidemiological research, including the UK Biobank, indicates regular glucosamine supplementation is correlated with a 15-39 percent lower risk of mortality from all causes.

“Increased risk of dementia is especially prominent in arthritis pain. Effectively treating pain is a critical part of decreasing Alzheimer’s risk, and this can be achieved by treating four key components of pain,” Dr. Teitelbaum said.

The Natural Products Association (NPA) also responded to the study, stating that while researchers disclosed these preliminary results would require human clinical validation, they “omitted a number of key confounding factors.”

“There is no conclusive evidence that glucosamine dietary supplements increase the likelihood of death within a specific time frame or accelerate progression from mild cognitive impairment to Alzheimer’s disease,” said NPA President and CEO Daniel Fabricant, PhD. “The researchers’ analysis of patients’ electronic health records does not establish causality, and they did not account for hidden variables or confounding factors, such as diets high in ultra-processed foods or advanced glycation end products (AGEs).”

Foods high in AGEs—usually heavily cooked, browned or highly processed meats and fats—contribute to oxidative stress and promote protein clumping in the brain found in Alzheimer’s patients, according to NPA.

“While the analysis controlled for age, sex and demographics, the study leaves too many unanswered questions about variables other than glucosamine supplements that may have contributed to a progression from mild cognitive impairment to dementia,” Dr. Fabricant said. “This includes but is not limited to frequent consumption of ultra-processed, sugary foods, which are theorized to accelerate the type of metabolic defect described in the study. Until human clinical research is conducted to eliminate such confounders, we urge consumers of glucosamine supplements to be circumspect about the study’s preliminary findings.”

For more information, visit www.npanational.org.