October 25, 2022

expert reaction to study of the effects of e-cigarette vapour on mice

A study published in Nature Communications looks at the effects of e–cigarettes on mice.

Prof Jacob George, Chair of Cardiovascular Medicine and Therapeutics at University of Dundee Medical School, said:

“The metabolism of mice is very different from humans and any extrapolation to overall, long-term human health is, frankly, guesswork at best. If this was indeed true, given the significant numbers of vapers worldwide, we would have expected to see an explosion in cardiac arrhythmia cases which we are not seeing in clinical practice, at all.

“The science is preliminary, the extrapolation is speculative and the relevance to human health, including around the nicotine effects on blood vessels, is highly questionable. Large human observational studies in nicotine replacement therapy users have shown that they do not increase cardiac event rates. The results of this study should not put off anyone wishing to quit tobacco smoking from trying e-cigarettes or nicotine replacement therapy. This early, pre-clinical study requires much more clinical correlation work in order to be considered relevant  to humans.”

Prof Peter Hajek, Director of the Tobacco Dependence Research Unit, Queen Mary University of London, said:

“In this study, mice were exposed to aerosol from e-cigarette solvents with and without nicotine and to acrolein, a chemical that can arise from overheated e-liquid. The exposures were accompanied by short-term changes in mice electrocardiograms and increased heart rate. 

“There are several problems with generalising the findings to humans. Vapers are not exposed to any significant levels of acrolein because overheated e-liquid has an unpleasant taste and so this is avoided. The study used exposure levels of the other chemicals that are tolerated by humans, but the same doses can be distressing to much smaller mammals with much more sensitive sense of smell and very different tolerance of drug effects. It would be odd if animals exposed to aversive stimulation did not show a cardiovascular response! The reason for conducting the study in mice is unclear. Animal models are used when the experiment cannot be conducted in humans, but there are no barriers to comparing heart rate and ECG responses to e-cigarette components and to smoking in humans.”

Prof Kevin McConway, Emeritus Professor of Applied Statistics at The Open University, said:

“I’m a statistician, not any kind of biologist, so I can’t comment on the physiological details of this research. Most aspects of the statistical analysis of the experimental results are solid, in my view, and the study provides good evidence that some of the components of e-cigarettes do have an effect on some aspects of the heart function in mice, when the mice are exposed to those components in the way that was done in this study. But, while I believe it’s definitely worthwhile to look at possible harmful effects of e-cigarette components, and I also believe that animal experiments can play a role in that work, there are important questions that this work can’t answer.

“I don’t think any knowledgeable commentators have ever suggested that human use of e-cigarettes is free of any harm. I think the important question is how the harm to someone who uses e-cigarettes them compares to the harm that would arise if that person didn’t use them. That clearly depends on what the person would do if they did not use e-cigarettes. If they were a smoker of conventional cigarettes, and if using e-cigarettes helped them to stop using normal cigarettes, then the e-cigarette use would have prevented the considerably greater harm from the person’s previous smoking habit. There’s evidence from several other studies¹ that e-cigarettes can be effective in helping people stop smoking cigarettes, and indeed that they are generally rather more effective than nicotine replacement therapy such as patches or gum. So, when used by someone who has a cigarette habit, really the important question is not whether vaping is entirely harmless, but whether it’s importantly safer than continuing to smoke cigarettes, or than using some other method to help them give up, which might be less effective. This new study can’t throw light on that question, and there’s certainly nothing in its findings to suggest that using e-cigarettes is as harmful as smoking normal cigarettes, even in mice.

“The comparison would be different in someone who wasn’t already a smoker, though one would need to consider whether using e-cigarettes might possibly change some other dangerous habit such as using a different drug.

“The fact that this research could, to an extent, separate out the effects of different components of e-cigarettes is a strength, in my view. Possibly that could lead to the development of safer e-cigarettes, for example. But, as the researchers point out, the responses to the various chemicals that they observed in mice may not be the same in humans, and though the research looked at several components of e-cigarettes and several different possible effects in the mice, it couldn’t look at everything relevant, so there’s more work to be done.

“Also, the number of female mice used in the study was low, just 4, and the female mice were not exposed at all to most of the types of substance involved. This means that some of the potential conclusions about there being a sex difference are not strongly based on evidence, as indeed the researchers themselves point out. Finally, the mice were (of course) all new to vaping, and the researchers point out that effects might well differ in humans who could be experienced users of e-cigarettes or tobacco.”

¹ https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub6/full

Dr Adam Jacobs, Senior Director of Biostatistics at Premier Research, said:

“This paper shows that mice exposed to e-cigarette aerosol in enclosed spaces for 90 minutes experienced short-term changes in cardiac rhythm. Although the long-term effects of these changes are not known, it seems prudent that owners of pet mice should not allow their mice to use e-cigarettes. For humans, although vaping cannot be considered entirely safe, there is abundant evidence that it is considerably safer than smoking combustible tobacco cigarettes, and therefore any smokers who switch from conventional cigarettes to e-cigarettes will be greatly reducing the risk to their health.”

‘E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice’ by Alex P. Carll et al. wa published in Nature Communications at 4pm UK time on Tuesday 25 October 2022, which is also when the embargo will lift.

DOI: https://doi.org/10.1038/s41467-022-33203-1

Declared interests

Prof George: “No interests to declare.”

Prof Hajek: “No conflict of interest.”

Prof McConway: “I am a Trustee of the SMC and a member of its Advisory Committee.  My quote above is in my capacity as an independent professional statistician.”

For all other experts, no reply to our request for DOIs was received.