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Evidence about electronic cigarettes: a foundation built on rock or sand?

BMJ 2015; 351 doi: (Published 15 September 2015) Cite this as: BMJ 2015;351:h4863

Rapid Response:

Laboratory studies contradict human epidemiology on carcinogenicity of nicotine

Krupp [1] suggests that my arguments about the non-carcinogenic effects of nicotine in my previous comment [2] are rhetoric rather than scientific. However, he still uses the same laboratory (cell or animal) studies to support his opinion that nicotine has carcinogenic effects. The only exception was a case control study of exposure to nicotine insecticide. Everyone knows, however, that nicotine used in e-cigarettes and in NRTs is pharmaceutical grade (according to USP or Eur. Ph.). Additionally, he probably did not notice the 2 characteristic examples I mentioned in my previous comment about the use of extremely high levels of nicotine in laboratory experiments which are irrelevant to realistic exposure of smokers [3,4].

There is no need to performed randomized trials asking participants to use a potentially harmful substance, as Krupp suggests. There is extensive epidemiological evidence derived from the long-term use of snus. Snus provides similar, if not higher amounts, of nicotine to users on a daily basis. Sweden has a high rate of tobacco use among men, but snus use by far exceeds smoking in this population [5]. As a result, Sweden has by far the lowest rates of lung cancer and cardiovascular disease than any other European country [5]. There is extensive epidemiological evidence that snus use poses (and in many cases no) risk in developing cancer and cardiovascular disease compared to NON-SMOKERS [6-8]. Considering that snus is a tobacco product which contains some toxins, it is more than evident that nicotine is highly unlikely to significantly contribute to the minimal adverse effects caused by snus. Thus, use of cleaner nicotine-containing products (such as snus or e-cigarettes) to substitute smoking will have tremendous health benefits for smokers. This should be clearly communicated to smokers. Although the ideal scenario would be to quit smoking without using any aid or to use approved smoking-cessation medications, the vast majority of smokers fail. Thus, we are ethically obliged to provide them with less harmful alternatives. It would be unethical to mislead smokers by distorting evidence and consider cleaner nicotine-containing products as equally or more harmful than smoking.

It is concerning that scientists completely ignore human epidemiological evidence but continue to support laboratory evidence. However, even laboratory studies have never shown than nicotine is equally or more harmful than smoking. Public health, as any other scientific field, should be based on unbiased presentation of evidence.

[1] Krupp K. Re: Evidence about electronic cigarettes: a foundation built on rock or sand? BMJ 2014. 351: h4863 (

[2] Farsalinos K. Evidence about nicotine toxicity and the dry puff phenomenon. BMJ 2014. 351: h4863 (

[3] Galitovskiy V, Chernyavsky AI, Edwards RA, Grando SA. Muscle sarcomas and alopecia in A/J mice chronically treated with nicotine. Life Sci. 2012;91:1109–1112.

[4] Bavarva JH, Tae H, Settlage RE, Garner HR. Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study. PLoS One. 2013 Jun 18;8(6):e67252.

[5] Ramstrom L, Wilkams T. Mortality attributable to tobacco among men in Sweden and other European countries: an analysis of data in a WHO report.

[6] Lee PN, Hamling J. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Med. 2009 Jul 29;7:36.

[7] Huhtasaari F, Lundberg V, Eliasson M, Janlert U, Asplund K. Smokeless tobacco as a possible risk factor for myocardial infarction: a population-based study in middle-aged men. J Am Coll Cardiol. 1999;34(6):1784-90.

[8] Hansson J, Galanti MR, Hergens MP, Fredlund P, Ahlbom A, Alfredsson L, Bellocco R, Engström G, Eriksson M, Hallqvist J, Hedblad B, Jansson JH, Pedersen NL, Trolle Lagerros Y, Ostergren PO, Magnusson C. Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival. J Intern Med. 2014;276(1):87-95.

Competing interests: Two of my studies on e-cigarettes (unpublished yet) were performed using unrestricted funds provided to the institution Onassis Cardiac Surgery Center) by e-cigarette companies in 2013.

08 October 2015
Konstantinos Farsalinos
Onassis Cardiac Surgery Center