A combination of caffeine and paracetamol could cause a risk to the liver, reported Metro and other news sources. It is “a hangover cure, used by millions of people worldwide – but mixing caffeine with paracetamol could be deadly”, it said. Combining “large quantities of the pain-killer and caffeine appeared to increase the risk of liver damage”, The Times explained, and “caffeine tripled the amount of a toxic by-product created when paracetamol was broken down”.
The stories are based on a laboratory study which examined the molecular structure of the enzyme that breaks down both paracetamol and caffeine.
As some newspapers report, the researchers have not calculated exactly what doses of the combination might have a harmful effect in humans and, as one expert told BBC News, "There are a million miles between E. coli and humans in terms of how paracetamol and caffeine are metabolised.”
The researchers advise people to use common sense: "We're not saying people should stop taking paracetamol or stop taking caffeine products but we advise that when taken together they should monitor the intake more carefully."
Dr Michael Cameron and colleagues from the Department of Medicinal Chemistry at the University of Washington in Seattle conducted this study. The work was supported in part by a grant from the National Institute of Health and was published in the peer reviewed journal Chemistry Research in Toxicology.
The study was a laboratory-based study that aimed to examine how caffeine affects the binding of paracetamol (also known as N-acetyl–p-aminophenol or acetaminophen in the USA) to a particular type of human enzyme (P450 3A4). In the body, this enzyme binds to paracetamol to break it down. This process produces a small amount of toxic byproduct that is then neutralised by the liver.
The authors describe how they obtained their chemicals (caffeine and paracetamol) and produced a purified version of the enzyme in genetically engineered bacteria (E. coli). They mixed paracetamol with the enzyme, either with or without caffeine present, and used nuclear magnetic resonance (NMR) spectrometry to show how the different chemicals were binding to the enzyme.
The authors showed that the addition of caffeine disrupts the way that paracetamol binds to the enzyme. This change in binding resulted in a three-fold increase in the production of the toxic byproduct of paracetamol.
The authors describe the chemistry of the binding and the interaction of caffeine and paracetamol in detail, but they do not interpret the significance of their findings.
Newspapers have reported later discussions with Professor Sid Nelson, the corresponding author for this study, and recommendations that people should limit the amount of coffee or energy drinks containing caffeine that they consume while taking paracetamol. They quote Professor Nelson as qualifying this by saying “the quantities of caffeine and paracetamol used in the study were far higher than most people would consume daily” and “the amount needed to produce a harmful effect in humans had not been calculated”.
This highly technical laboratory study has implications for how we understand the toxic effects of paracetamol. Demonstrating, at a molecular level, that there is co-operative binding between paracetamol and caffeine is important for understanding the first step in this chemical pathway.
However, the differences between what happens in the test tube and the evidence required to give meaningful advice to the many people who drink small quantities of caffeine or take standard doses of paracetamol, or both, are vast.
As the researchers advise in the newspaper reports, there is no reason to stop taking caffeine products and paracetamol, but when taken together “they should monitor the intake more carefully."
There are many hangover “cures”; Jeeves once gave Bertie Wooster a raw egg, red pepper and Worcester sauce, as far as I remember.
Both these drugs, caffeine and paracetamol are powerful and two powerful drugs together can sometimes be more powerful than the sum of their individual effects; in this case, as so often, prevention is probably better than cure.