Glucosamine is a popular supplement used regularly by millions of people worldwide for osteoarthritis and joint pain, and until recently, studies seemed to indicate that it was safe to use, even if its effectiveness in improving joint pain is slight, reports The Washington Post.
But Raquel Largo, a senior rheumatology researcher at the Jiménez Díaz Foundation in Madrid, believes there are lots of controversies regarding the real effect of glucosamine – and recent research may be concerning to those who use it.
A study published in Nature Metabolism adds a potential finding that people with Alzheimer’s or their caregivers may want to take into account when considering glucosamine, said Largo, who was not involved in the study. The researchers found that using glucosamine may be linked to accelerated progression and higher mortality in Alzheimer’s disease and related dementias.
Whether that is true or not – and many questions remain – the study does raise an important point: if people have any signs of dementia, “they really should be talking to a doctor about what they take and not take”, said Ramon Sun, an associate Professor of Biochemistry at the Department of Molecular and Cellular Bochemistry at the University of Florida and senior author of the study.
“There are so many things that we don’t know that will accelerate the disease or reduce the disease,” he added.
The science behind the new research
In the study, Sun and his colleagues analysed clinical records from almost 25 000 patients diagnosed with Alzheimer’s and related dementias. They found that patients who had documented use of glucosamine for at least a year after their diagnosis were 25% more likely to die in the next 10 years than patients who did not use glucosamine.
In contrast, using glucosamine did not increase mortality risk in patients with mild cognitive impairment, an intermediary stage between healthy ageing and dementia. But using glucosamine was linked with a 25% higher chance of progressing from mild cognitive impairment to dementia.
The research did not look at healthy participants, but previous studies of glucosamine use in the general population did not demonstrate worsening of any disease, Largo said. (In fact, some research suggests glucosamine is linked to reduced cardiovascular and all-cause mortality, possibly because of reduced inflammation.)
When people take glucosamine, “the majority of it will come out as urine”, Sun said, “but there is a small percentage that will get into the cells and it becomes these sugar chains outside the cells. And that is universal. It’s the brain, the knee, the liver: it does it everywhere.”
These sugar chains, known as glycans, are attached to proteins and important for cellular function – and not just for energy. In the brain and nervous system, glycans are essential for neuroplasticity and proper neuronal communication. Too much or too little may not be good for brain function, Sun said.
When the researchers gave glucosamine to mice that carried Alzheimer’s disease-related genes, their social memory worsened and there were signs of increased glycans; this was not the case for mice without those genes that were given the supplement. Conversely, blocking an enzyme that synthesises glycans improved the mice’s social memory.
But there are also major limitations to that study that call for additional research. The data linking glucosamine use and faster progression of dementia in humans is correlational and cannot show causation, and the researchers only accounted for sex, age and ethnicity as potential confounding factors that could explain the association, said Angela Zivkovic, a nutrition Professor at the University of California at Davis who wasn’t involved in the study.
For example, people who take glucosamine because of joint pain may move less and be more physically frail, which is associated with higher dementia risk, Zivkovic said.
Researchers for the new study used a cutting-edge technique called spatial metabolomics to map out the amount of glycans in brains of Alzheimer’s patients as well as mice with Alzheimer’s-related genes, and they reported these brains had more glycans than healthy brains.
But the available techniques don’t make it possible to know if there is a general overabundance of glycans in the brain and how that is linked to dementia, Zivkovic said.
“They used a really cool tool but applied it in a way that kind of missed a lot of the underlying biology.”
This kind of research is difficult to study because there are so many kinds of glycans that perform different functions.
“Glycomics is … sort of like the last frontier, and we have very little understanding of how it works,” Zivkovic said.
Does glucosamine help joint pain?
The evidence that glucosamine helps osteoarthritis pain is mixed at best, experts said. Meta-analyses of previous studies tend to find that glucosamine has a “slight effect on pain” – when there was a statistical effect at all, Largo said.
Studies from larger, randomised controlled trials, the gold standard of biomedical research, find that glucosamine does not perform better than placebo.
“There is really no good double-blind placebo control study that shows that glucosamine is actually effective at minimising joint pain,” Sun said. (The location of the osteoarthritis pain may matter: Largo said there is some research suggesting glucosamine may have a “moderate” effect on pain in the knee.)
Likewise, some studies suggest that glucosamine may help the structure of the joint, but the benefit is slight, she added.
As a result, many medical organisations do not recommend glucosamine for osteoarthritis patients.
Despite the lack of good evidence for glucosamine’s effectiveness, there is a reason the millions of osteoarthritis patients may still turn to it: There are few options for everyday pain or treatments to slow the progression of the disease.
NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin and ibuprofen, are the only medications that are recommended. While they can be effective at controlling pain in the short-term, NSAIDs aren’t the best medications to use continuously. They come with their own risk of side effects and can be dangerous for older people or those with gastrointestinal problems, Largo said.
Funding for osteoarthritis research is low, despite the condition’s prevalence, because unlike cancer or dementia, for example, it does not kill you, at least directly, Largo said.
But osteoarthritis can not only lower quality of life: it can also cause people to move less, have problems working and increase risk for depression, cardiovascular issues and weight gain – which all have an impact on longevity.
There needs to be additional research into the link between glucosamine and Alzheimer’s disease, experts say. “But the other side of the coin is: is it worth it risking to take glucosamine, especially if it doesn’t really help with the joint pains at all?” Sun said.
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