Experts call for clinical trials to validate joint supplement's link to CVD risk

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A report claiming glucosamine supplement use relates to lower cardiovascular (CVD) event risk has been met with a cautious welcome by medical experts, who urge the need to establish cause and effect.

Writing in the British Medical Journal (BMJ), the report states that habitual use of these supplements, normally used to relieve osteoarthritis pain, may also aid in lowering total CVD event risk by 15%.

The report adds that the supplement’s use is linked to a 9%-22% lower risk of individual CVD events such as CVD death, coronary heart disease, and stroke.

Concurring with the study authors, Naveed Sattar, professor of metabolic medicine at the University of Glasgow agreed that further clinical trials were needed to test this hypothesis.

“Whilst the authors have done a careful job of analysing the link between glucosamine intake and cardiovascular outcomes in a big dataset, only a trial can determine whether there is any truth to the lower observed risk,” he said.

“Observational studies can only ever generate new ideas to test.  They cannot prove a causal link since some biases are impossible to overcome and it may well be those who take glucosamine regularly have healthy lifestyles in ways that are not fully captured by measured data.”

UK Biobank data

The report cites recent evidence from animal studies and cross sectional studies in humans that suggest glucosamine could have a role in preventing CVD and a mortality reduction.

However, the team, which drew upon genetic and phenotypic data from the UK Biobank, added that evidence from prospective studies was lacking.

Further action saw 466 039 participants without CVD at the start of the study enrolled. These participants, who completed a questionnaire on supplement use, which included glucosamine, were enrolled from 2006 to 2010 and were followed up to 2016.

During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events.

After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events, CVD death, coronary heart disease and stroke.

“In this large prospective study, habitual glucosamine use was associated with a 15% lower risk of total CVD events and a 9%-22% lower risk of individual cardiovascular events (CVD death, CHD, and stroke),” the researchers said.

Smoking status

The team, hailing from the US and China, added that such associations were independent of traditional risk factors, including sex, age, body mass index, healthy diet, smoking status and other supplement use amongst others.

“In addition, we found that the associations between glucosamine use and CVD outcomes were statistically significantly modified by smoking status.”

The team also put forward a series of potential mechanisms that could explain the observed protective relation between glucosamine use and CVD diseases.

These include the regular use of glucosamine’s association with a reduction in C reactive protein concentrations, a marker for systemic inflammation. 

In addition, a previous study found that glucosamine could mimic a low carbohydrate diet by decreasing glycolysis and increasing amino acid catabolism in mice, strengthening arguments that glucosamine mimics an energy restriction agent.

Other explanations include observations that identify low carbohydrate diets’ link to a reduced risk of CVD in epidemiological studies as well as an observed protective effect against CVD development.

Cause and effect

Dr Sonya Babu-Narayan, associate medical director at the British Heart Foundation said the observational study suggested associations rather than cause and effect. 

“We don’t know whether people who took glucosamine were less likely to develop cardiovascular disease because of the glucosamine itself, or if other factors were at play,” she said.

“For example, people who take glucosamine might be more likely to look after their health in general. Ultimately, controlled clinical trials will be needed to uncover whether glucosamine is beneficial in preventing heart and circulatory diseases.

“If a well-known and widely available supplement like glucosamine could help prevent heart and circulatory diseases, including heart attack and stroke, it is an avenue of research worth exploring.”

Source: The BMJ

Published online: doi.org/10.1136/bmj.l1628

“Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank.”

Authors: Hao Ma et al