EXPERT REACTION: Joint supplement may be good for your heart

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Regular use of glucosamine supplements, which are normally taken to help joint pain, may help lower your risk of heart disease, according to international research. The study used data on almost half a million British men and women and found that those who used glucosamine had a 15 per cent lower risk of cardiovascular disease events overall. The benefit among smokers was more than double that of non smokers. The study is observational - so it cannot show cause and effect, but the researchers say this link could be explained by the effects of glucosamine on inflammation, which plays a role in both cardiovascular disease and arthritis.

Journal/conference: The BMJ

Link to research (DOI): 10.1136/bmj.l1628

Organisation/s: Tulane University, New Orleans, USA

Funder: LQ was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616). SHL is partially supported by grant P20GM109036 from the National Institute of General Medical Sciences of the National Institutes of Health.

Media Release

From: The BMJ

Glucosamine supplements may be linked to lower risk of cardiovascular disease

Findings suggest possible preventive role, but further trials needed to test this theory

Regular use of glucosamine supplements may be related to a lower risk of cardiovascular disease (CVD) events, suggests an analysis of data from the UK Biobank study, published in The BMJ today.

The findings suggest that glucosamine may have benefits in preventing CVD events, such as coronary heart disease and stroke, and further clinical trials are needed to test this theory, say the researchers.

Glucosamine is a popular dietary supplement used to relieve osteoarthritis and joint pain. While its effectiveness on joint pain continues to be debated, emerging evidence suggests that glucosamine may have a role in preventing cardiovascular disease and reducing mortality. However, conclusive evidence is still lacking

So to explore these potential associations further, researchers led by Professor Lu Qi at Tulane University in New Orleans drew on data from the UK Biobank - a large population based study of more than half a million British men and women.

Their analysis included 466,039 participants without CVD, who completed a questionnaire on supplement use, including glucosamine.

Death certificates and hospital records were then used to monitor CVD events, including CVD death, coronary heart disease (CHD), and stroke, over an average seven-year follow up period.

Overall, almost one in five (19.3%) participants reported glucosamine use at the start of the study.

The researchers found that glucosamine use was associated with a 15% lower risk of total CVD events, and a 9% to 22% lower risk of CHD, stroke, and CVD death compared with no use.

These favourable associations remained after taking account of traditional risk factors, including age, sex, weight (BMI), ethnicity, lifestyle, diet, medication and other supplement use.

The association between glucosamine use and CHD was also stronger in current smokers (37% lower risk) compared with never (12%) and former smokers (18%).

Several mechanisms may explain these results, say the authors. For example, regular use of glucosamine has been linked to a reduction in levels of C-reactive protein (CRP), a chemical associated with inflammation. This may also help to explain the stronger association among smokers, who have higher levels of inflammation and higher risk of CVD than non-smokers.

In addition, previous data suggest that glucosamine may mimic a low carbohydrate diet, which has been inversely associated with the development of CVD.

Despite the large sample size, this is an observational study, and as such, can’t establish cause, and the researchers point to some limitations, such as lack of information on dose, duration, and side effects of glucosamine use.

Regular glucosamine use may also be a marker for a healthy lifestyle, they add, but this is unlikely to have affected the results.

As such, they conclude that “habitual use of glucosamine supplements to relieve osteoarthritis pain might also be related to lower risks of CVD events. Further clinical trials are warranted to test this hypothesis.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

The key words in the paper are, 'Habitual use of glucosamine supplement to relieve osteoarthritis pain might be related to lower risks of CVD events. Further clinical trials are needed to test this hypothesis'.
Also, 'We could not exclude the possibility that the observed inverse associations were driven by healthy lifestyle factors among glucosamine users, although we had carefully adjusted for potential confounding in our analyses'.
Questions about diet, exercise and other life-style factors were apparently only asked twice and may well have changed over time. It is also not clear how they handled life-style results that changed from the first visit (12 December 2009 to 7 June 2013) and the second visit (between 30 April 2014 and 10 August 2017).
Results were expressed as relative risk, not absolute risk, 'glucosamine use was associated with a 15% lower risk of total CVD events and a 9%-22% lower risk of individual CVD events (CVD death, coronary heart disease, and stroke'. This is potentially misleading, figures on absolute risk (CVD events, deaths, etc, per 1000 patients per year in glucosamine users compared to non-users) should also have been given.
Finally, glucosamine is no longer recommended for osteoarthritis: https://www.nice.org.uk/donotdo/do-not-offer-glucosamine-or-chondroiton-products-for-the-management-of-osteoarthritis. Thus, it is unlikely that this study will be replicated and, in my opinion, a large-scale controlled clinical trial to test what is at best a dubious hypothesis is unlikely to get up.

Last updated: 18 Nov 2019 11:59am

Declared conflicts of interest:

None declared.

Peter Clifton is an Adjunct Research Professor of Nutrition at the University of South Australia

Although it is likely the observation of reduced heart disease risk in glucosamine consumers is due to unmeasured confounders as the glucosamine group was a healthier group (and even exercised more despite the apparent need for glucosamine) and a more affluent group, there is a small amount of evidence that glucosamine may be biologically active.
A previous study showed reduced C-Reactive Protein (CRP) - a protein that is made in the liver and secreted into the blood and is a marker of inflammation- in healthy overweight and obese participants (n=18) taking 1.5g glucosamine and 1.2g of chrondoitin for 28 days.
In addition, by studying the change in the amount of proteins in blood , the research showed a reduced "cytokine activity pathway" - a group of proteins that are important in cell communication and cell contact. So it is possible that glucosamine may reduce the inflammatory reaction in arteries.
Previously glucosamine consumption has been linked to lower total and cancer mortality.
In one of these studies, which was much smaller than BioBank, heart disease was reduced by a similar amount but this failed to reach clinical significance. Time for a secondary heart disease prevention study with glucosamine.

Last updated: 14 May 2019 5:42pm

Declared conflicts of interest:

None declared.

Dr Louisa Lam is Deputy Dean of the School of Nursing and Healthcare Professions at Federation University Australia

There are so much controversial around the effects of Glucosamine and vitamin supplements in general, I do have doubt with the analysis. There are lots of research evidence supports my doubt.

Please see one example below:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035477/

My view is, the study has a very large sample, with large sample like that, it is easy to find some statistical significance in ‘things’ the researchers want. Huge samples can make the Insignificant…Significant!

Please see below link on problems with large sample size:

https://blog.minitab.com/blog/statistics-and-quality-data-analysis/large-samples-too-much-of-a-good-thing

I would really like to see the association of other supplement to CVD event or death. The authors should provide information on other supplements as comparisons. Also, a Yes and No answer on the use of Glucosamine is insufficient. We need dose and length information. I have doubt on the reported result in relation to the link between glucosamine supplement and lower risks of CVD events.

Last updated: 14 May 2019 3:58pm

Declared conflicts of interest:

None declared.

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