Heat not burn products similar to smoking for heart disease? Confusing acute nicotine effects with long-term smoking effects


By Dr Farsalinos

An abstract at the American Heart Association Scientific Sessions evaluated the acute effects of exposing mice to a heated tobacco product (IQOS) on endothelial function in comparison with a tobacco cigarette. The study found that IQOS had the same adverse effects on Flow-Mediated Dilatation (FMD), a marker of endothelial function, as the tobacco cigarette. The abstract concluded that “Use of HNB tobacco products does not necessarily avoid the adverse cardiovascular effects of smoking cigarettes”. The poster was, as expected, accompanied by a press statement which concluded with a similar statement: “Using heat-not-burn products may not avoid the adverse cardiovascular effects of smoking cigarettes”.


Although FMD (and other measures of vascular function) have no prognostic value when measured after an acute exposure, the abstract itself could be considered alarming and create some concern. Of course, there has been some publicity on it already. But we all know that “the devil is in the detail”. In this case, some critical information omitted from the abstract is mentioned in the press statement (and in the presented poster to which I have access).


The poster mentions some very interesting information. For the same exposure in terms of duration and puff number, IQOS delivered 4.5 times MORE nicotine to the mice compared to tobacco cigarettes. So, the comparison was between exposure to the tobacco cigarette resulting in 15 ng/mL plasma nicotine levels, versus exposure to the IQOS resulting in 70ng/mL plasma nicotine levels. This creates two fundamental problems with this study, which makes the conclusions of the abstract and press statement problematic.


First, in laboratory studies it is crucial to compare equivalent exposures. In this case, I suppose none can consider the 4.5-fold difference in plasma nicotine levels as equivalent exposure. Secondly, the fact that IQOS delivered so much higher nicotine levels compared to the tobacco cigarette is not only bizarre but also contrary to all available evidence. In June 2017, I published a study measuring nicotine delivery to the aerosol of IQOS and to the smoke of a commercial tobacco cigarette (the same brand as used in the mice study). We found that, at 2 different puffing regimes (changing puff duration only), IQOS delivered about 30% less nicotine to the aerosol compared to the tobacco cigarette. Recently (July 2017), a research group led by Dr Bekki and Dr Kunugita from the Japanese National Institute of Public Health found that IQOS delivers 30% less nicotine to the aerosol compared to a standardized tobacco cigarette (3R4F). The manufacturer of IQOS published a study in 2016 showing that it delivers (you probably guessed it right) 30% less nicotine compared to a standardized tobacco cigarette (3R4F). So, this amazing consistency from 2 independent and one industry research groups is suddenly challenged by a study showing 4.5 times more nicotine delivery from the IQOS. Obviously, either the 3 chemical studies are completely wrong or something went wrong during the exposure of mice to IQOS and tobacco cigarette.


There is another error, fundamentally linked to the abstract methodology, results and conclusion. It is a fact, observed in humans, that nicotine itself (in the form of NRT-nasal spray) has an adverse effect on FMD. The authors found that, for the same plasma nicotine levels, NRTs had a significant but lower adverse effect compared to smoking. So, what would happen if the NRT delivered 4.5 times higher nicotine levels compared to the tobacco cigarette in this study? We can only make a reasonable assumption. Acute adverse effects on FMD have been observed with other stimulants too, such as (you probably guessed that too) caffeine.


In conclusion, the study found that IQOS has the same acute adverse effect on FMD as cigarettes when delivering 4.5 times higher amount of nicotine compared to the tobacco cigarette. This should have been the study conclusion, but this information was not even mentioned in the abstract (however, it was presented in the poster). Considering that a substantial part of acute adverse effects on FMD is caused by nicotine itself (with nicotine having minimal, long-term cardiovascular risk), in my opinion, this is almost clear evidence that IQOS has a lower acute adverse effect on FMD than smoking (it would have been perfectly clear if the nicotine exposure to mice was similar). In fact it is possible that this adverse effect is caused by nicotine alone. Due to the assessment of an acute effect on FMD, the study has no prognostic value for cardiovascular disease risk. NRTs have the same acute effects on FMD, but they are approved for long-term use as smoking substitutes (by both FDA and MHRA). Finally, I have strong concerns about the experimental procedure because it is impossible for IQOS to deliver more nicotine than a tobacco cigarette with the same puffing regime (at least in humans).

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