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expert reaction to study looking at salt in soluble paracetamol and risk of heart disease

A study published in the European Heart Journal looks at sodium in soluble paracetamol and cardiovascular outcomes.


Prof Tom Sanders, Professor Emeritus of Nutrition and Dietetics, King’s College London, said:

“This is an interesting finding from an observational study suggesting an adverse effect of paracetamol in an fizzy dosage formulation than contains more sodium, mainly in the form of sodium bicarbonate.  The health concerns surrounding sodium are its association with salt intake and high blood pressure.  Randomised trials have not found sodium bicarbonate to increase blood pressure, which is in contrast to sodium chloride (salt).

“What is not clear from this study are the reasons why some patients were prescribed the fizzy formulation and others the non-fizzy form.  Fizzy formulations are preferred where patients have stomach acid reflux.  It is possible that patients with acid reflux are more at risk of cardiovascular disease rather than an effect of the paracetamol formulation.  The answer could be found by conducting a proper randomised controlled trial for the fizzy paracetamol formulation versus the non-fizzy version.”


Catherine Collins, NHS dietitian, said:

“The sodium content of medicines is something we frequently look at when advising people with heart failure, kidney impairment or liver disease on the optimal diet to control their health issues.  Common to these conditions is a risk of fluid overload, which can be worsened with a high sodium intake.  It’s not uncommon to find the sodium content of medicines contributing the equivalent of over 10g salt a day, especially in those patients taking the maximum daily dose every day.  A good daily goal for salt is around 6g per day (or 2400mg sodium).

“Conversely, we sometimes exploit the sodium content of prescribed medicines – soluble or effervescent paracetamol can provide a handy sodium load to help people with an ileostomy absorb more of the fluid from their dietary intake, preventing dehydration.  Ileostomists have greater sodium losses each day, so the impact of a higher salt intake is moderated when compared with the general population.

“There are people who are unable to swallow tablets so need to take dissolvable medications.  For those patients it’s important not to halt their medications simply on these findings, given the authors admit their data is incomplete – daily dietary salt intake wasn’t measured and although death rates were measured, actual cause of death may have related to something entirely irrelevant to their study – for example if someone died in a road traffic collision, rather than as a result of a fatal heart attack on a background of poorly managed high blood pressure and a high sodium intake.

“We also know that chronic pain and inflammation influences not only diet but how the body responds long term.  Was risk of death associated with use of a sodium containing painkiller?  Or to the underlying health condition causing pain that was the reason for you talking them in the first place?  Did that person have a poorer quality diet due to pain issues preventing them from cooking or buying healthier foods which might have also contributed long term to poorer overall health?  It’s impossible to separate out this necessary detail from the study information collected.

“For the general public it’s also useful to recognise that many popular ‘fizzy’ vitamin supplements also contain a significant amount of sodium, which most people aren’t aware of.  Some manufacturers have changed their formulations over the past few years, but there’s many ‘fizzy’ supplements that still provide sodium – sodium bicarbonate / sodium carbonates will be listed high on the ingredients label.  This isn’t always obvious from the front of pack labelling, hidden by the ‘health halo’ of taking a vitamin supplement.  Tablet versions will naturally be low in sodium, so if in doubt, choose these instead.”


Dr Richard Francis, Head of Research at the Stroke Association said:

“Paracetamol in pill, capsule or oral suspension (bottled liquid) form doesn’t usually contain any salt, but the soluble, fizzy paracetamol that you add water to does.  If you had the maximum daily dose of soluble paracetamol, your salt intake from that alone would be over the daily recommended limit.  In this study, people who were prescribed soluble paracetamol had more strokes in the year after it had been prescribed than those who were prescribed capsule or tablet forms, regardless of whether they had a history of high blood pressure.

“We don’t know from this study why people were prescribed soluble paracetamol and we don’t have a comparison against people who don’t take paracetamol at all, so we don’t know how many of the more at risk groups’ strokes could have been increased by other risk factors.  This means that we can’t really apply the findings from this study to broader groups of people.

“What we do know is that pill, capsule, and oral suspension (bottled liquid) forms of paracetamol don’t usually contain salt, so these findings shouldn’t be too concerning for people choosing these forms of over-the-counter paracetamol.  People who have been prescribed salty, soluble paracetamol should have its salt content made clearer to them, try to reduce the salt content in the food they eat, work with their doctor to manage their blood pressure and try to switch to a type of paracetamol without salt.”


Prof Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:

“Eating too much salt can increase blood pressure.  Cutting down on salt in our diets is an important way we can help to keep our blood pressure under control and reduce our risk of having a heart attack or stroke.  However, this large analysis suggests that people who take some types of paracetamol may have inadvertently been consuming too much sodium, one of the main components of salt.

“One important limitation of this study is that we don’t know how much salt people were already consuming in their diets, as this was not captured in the data analysed.  This means we don’t know whether there were any differences in salt consumption between the groups which could have affected their risk of developing a heart and circulatory condition or dying.

“It’s also important to remember that observational studies like these can only show an association, rather than prove cause and effect.

“This research looked at people who were taking effervescent and soluble paracetamol over a longer period.  If you take paracetamol that contains sodium occasionally to manage an isolated headache or very short bouts of pain, these research findings should not cause unnecessary concern.”


Prof Tim Chico, Professor of Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Sheffield, said:

“This is a well conducted study.  It shows the power of using NHS data to do research of public benefit.  To know whether or not sodium containing medications increase risk of disease in a randomised trial would be difficult and hugely expensive, so is unlikely ever to be performed.  This means we need to also use NHS data from routine healthcare to help guide medical decisions.

“Because this was not a randomised study (where people are allocated to take sodium or non-sodium containing paracetamol) it’s not possible to conclude firmly that the sodium-containing versions directly increase risk of death and heart disease.  However, the circumstantial evidence this study provides does raise a real concern that they might.  It makes sense that regularly taking sodium-containing paracetamol over extended periods of time could increase risk of heart disease and death based on evidence from other studies that compare salt intake with future health.

“It would be helpful to perform similar studies in other healthcare databases to understand how reliable the findings are.  However this study makes me more cautious about prescribing sodium-containing paracetamol (or other sodium-containing medications) for long-term use.  Unless there is a very good reason people can only swallow soluble forms of the medication, it is possible they might be safer using the non-sodium containing versions.”



‘Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension’ by Chao Zeng et al. was published in the European Heart Journal at 00:05 UK time on Thursday 24 February 2022.

DOI: 10.1093/eurheartj/ehac059



Declared interests

Catherine Collins: “No conflict of interest declared.”

Prof Tim Chico: “No conflicts.”

None others received.



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