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A common supplement for joint pain may speed up dementia progression, a new study suggests. Image credit: Antonio Hugo Photo/Getty Images
  • Osteoarthritis, which leads to joint pain, swelling and stiffness, occurs in more than one-third of people over the age of 65.
  • Many of these will be prescribed, or will buy, glucosamine supplements, which may help to ease the symptoms.
  • However, a new study suggests that glucosamine could speed the progression of dementia and even increase mortality in people with dementia.
  • As glucosamine is such a widely used supplement, the researchers call for more research to verify their findings.

Joint pain, swelling and stiffness become increasingly likely as we age, and these symptoms may be due to osteoarthritis, which affects one-third of people over the age of 65.

Οne popular supplement for osteoarthritis is glucosamine sulfate, which people take to alleviate pain and stiffness.

According to one study, around 6-7% of people over the age of 70 in the United States are prescribed glucosamine to relieve symptoms.

Many more buy it without prescription as a dietary supplement, despite there being little study evidence for its efficacy.

Now, a new study has found that glucosamine may speed the progression of dementia and hasten mortality, by enhancing a process in the brain that is overactive in people with Alzheimer’s disease.

The study, which is published in Nature Metabolism, suggests that glucosamine may increase hyperglycosylation — a process that impairs the function of nerve cells in the brain.

Harris A. Gelbard, MD, PhD, Director of the Center for Neurotherapeutics Discovery, and Professor in the the Departments of Neurology, Pediatrics, Neuroscience and Microbiology and Immunology at the University of Rochester Medicine, not involved in this research, commented on its findings to Medical News Today:

“Their study carries enough weight to further define the relationships between age of onset of glucosamine supplementation and specific types of dementia. This is especially true with respect to their findings of accelerated mortality since patients with late onset dementia can live a relatively long time, albeit in a cognitively impaired state.”

The researchers analysed samples from post-mortem human brain tissue, from people with and without Alzheimer’s disease.

They found that brains from people with Alzheimer’s disease showed a pattern of increased synthesis of glycans — carbohydrate molecules that attach to proteins and change their function. The later the stage of Alzheimer’s, the higher the production of glycans.

Gelbard explained how hyperglycosylation can affect the functioning of nerve cells, and speed Alzheimer’s disease damage.

“Key to understanding this is the observation from the present study that these changes occur after clinical evidence of cognitive decline as opposed to the early asymptomatic or mild phases,” he told MNT.

“Hyperglycosylation can greatly increase the brain burden of sugar molecules called N-glycans that overload metabolic processing and disrupt critical cellular processes like synaptic signaling (sending messages between neurons) in regions of the brain devoted to learning and making new memories,” Gelbard explained.

“As these N-glycans continue to accumulate in the brain,” he continued, “this leads to destruction of synapses [connections between nerve cells], with the potential to activate the immune system and create a vicious cycle of brain damage.”

The researchers carried out experiments in mice genetically modified to develop two different forms of Alzheimer’s disease.

They found similar patterns of hyperglycosylation to those seen in human brains, with most hyperglycosylation in regions associated with memory, cognitive processing and neuroinflammation, the areas that show most neurodegeneration in Alzheimer’s disease.

They established that this was a result of increased glycan synthesis, rather than impaired breakdown of glycans in the brain.

When they blocked glycan formation in mice, the mice performed better in memory tests.

Glucosamine can easily cross the blood-brain barrier and is incorporated into brain glycans, so the researchers tested, in mice, whether glucosamine speeded up degeneration of nerve cells.

In mice with the 5xFAD version of Alzheimer’s disease, glucosamine supplementation significantly increased glycan production and worsened social memory.

Gelbard cautioned that, while their methodologies were sophisticated, appropriate and robust for this study, the researchers were using an aggressive model of Alzheimer’s.

“The use of the 5xFAD model represents an aggressive, accelerated dementia phenotype of EOAD (early onset Alzheimer’s dementia) and thus represents a relatively small percentage of Alzheimer’s disease in general (i.e., LOAD or late onset Alzheimer’s dementia),” he told MNT.

Courtney Kloske, PhD, director of scientific engagement for the Alzheimer’s Association, likewise not involved in the study, summarized:

“In this study, researchers found that glucosamine appeared to increase activity in a biological process that may contribute to Alzheimer’s disease, and was associated with worsening memory outcomes in animal models.”

To assess whether glucosamine might have similar effects in people, the researchers analysed data from more than 50,000 people with Alzheimer’s-disease-related dementias (ADRD) in the University of Florida Health system.

They identified people who had used glucosamine supplements for at least a year after a dementia diagnosis then compared them with people who had been diagnosed with mild cognitive impairment (MCI), a small reduction in memory and thinking skills which often precedes dementia.

They identified 24,481 patients with ADRD and 41,884 patients with MCI for the survival analysis, and followed them up for a mean of around 5 years. Of this group, 1,896 patients with ADRD and 2,750 patients with MCI, approximately 8%, had taken glucosamine.

They found that glucosamine use was associated with a 25% increase in mortality risk among ADRD patients, but that there was no increase in mortality risk in people with MCI.

“The evidence is compelling enough, even with the limitations I mentioned, to have physicians suggest a cautionary note in self-medication with neutraceuticals,” Gelbard advised.” It further emphasizes the need for biomarker studies in patients with family histories of dementia to perform watchful waiting.”

Kloske stated that more research was needed, adding that “the results should not be interpreted as a recommendation to start or stop glucosamine or any other supplement without first consulting a healthcare provider.“

“While these findings add to our understanding of the potential relationship between glucosamine, brain health, and Alzheimer’s disease progression, the data do not establish cause and effect,” she cautioned.

She further advised: “A growing body of research suggests that healthy dietary patterns and balanced nutrition may help support overall brain health and may contribute to reducing the risk of cognitive decline. However, no single food, beverage, ingredient, vitamin, or supplement has been proven to prevent, treat, or cure Alzheimer’s disease or other dementias. “

“The most important takeaway for consumers is to have informed conversations with their healthcare team before starting, stopping, or changing any supplements.”

– Courtney Kloske, PhD