Diacetyl in e-cigarettes — what we can really say (not much)

by Carl V Phillips

I received an inquiry about diacetyl from a reporter in the e-cigarette press and though I would share my response more widely. Most readers will know that diacetyl is a food additive that produces a strong buttery flavor, and that it is the most controversial among the several controversial flavoring agents in e-cigarettes. The concern is that high-dose inhalation exposure is believed to produce the horrible acute lung disease, bronchiolitis obliterans, commonly known as “popcorn lung” because the cases have been found in workers in flavored popcorn factories and at least one consumer who was huffing the outgassing from microwaved popcorn. (I say “believed” because all of these victims inhaled a cocktail of chemicals, not just the one molecule, so it is consistent with the evidence that the outcome depends on the multiple exposures and is even possible that diacetyl is not a necessary part of the mix.)

My regular readers might also recall that elsewhere I have referred to the diacetyl controversy as an own goal. It was vapers and e-cigarette advocates who introduced the worries about this molecule, which is quite reasonable, but then managed to build the level of consternation well above what was suggested by the evidence. The most important bit of evidence is that after many millions of person-years of vaping, some unknown but nontrivial portion of which included diacetyl exposure, there has not been a reported case of a vaper getting bronchiolitis obliterans. Those who follow the anti-vaping propaganda will no doubt know that the anti-THR liars have picked up on the consternation as their latest claim — “Vaping causes popcorn lung!!!” Never mind that it hasn’t done so.

Anyway, the science is complicated and there are no simple answers. The evidence is consistent with diacetyl in e-cigarette liquid being hazardous, and with it being the most hazardous single characteristic among e-cigarettes (there is nothing that we know poses a measurable risk for any serious disease). The evidence is also consistent with this exposure causing no risk at the relevant quantities.

I balked at answering the series of set-piece questions in the reporter’s query. I was not comfortable answering some of them because they embed premises in the questions that any answer would implicitly endorse. Others were difficult technical questions that no one, as far as I know, has the expertise to answer, or that would require an entire paper to provide a scientifically legitimate answer. So instead I offered the following response:

The framing of the discussion surrounding diacetyl in the vaper community is misleading in several ways. First, it is extremely difficult to estimate risks from consumer exposures based on occupational epidemiology results, which generally involve extreme levels of exposure and a cocktail of different exposures rather than just a single chemical. It is far more difficult to estimate real risks based on artificial toxicology experiments. Both extrapolations involve heroic guesses. One such guess is about the dose-response, a concept that seems to be widely understood among those discussing the issue. But other guesses are even more difficult than that, including how different exposures interact (no one is being exposed to just one molecule, either vaping or in an occupational setting), and how particular subpopulations might react. Fortunately we know from real-world experience that widespread e-cigarette use, for a period of a several years, has not caused any detectable outbreaks of any serious acute disease including the one that is popularly attributed to diacetyl exposure. That is the most solid evidence we have.

However, inhalation of anything other than clean air may cause risk. Eliminating one molecule, or ten, from vapor is not going to change that. We know enough from vapor chemistry and epidemiology to be reassured that for normal vaping, there is no known major hazard. But we do not know nearly enough about the interaction of airway biology and this concentration of exposure over decades (even for the very benign chemicals, like the carriers) that we can be confident we have identified potential harm pathways. Obviously any risks are dwarfed by those of smoking; those of us who have made educated guesses about the risk put it in the range of 1/100th that from smoking. But though the “we just don’t know anything!” rhetoric we have to deal with is clearly absurd, there is genuine uncertainty. It would be surprising if the risk were as high as 3% that from smoking and astonishing if it was 5%. But given the complexity of biology it is possible that long-run exposure causes that much risk or even more, particularly for more harmful combinations of liquid chemistry, hardware, and behavior. (Note that we do not really know which of those are more harmful, though we can make some guesses — we can just be sure that some are worse than others.)

We can expect that some particular chemicals and technologies (e.g., being able to overheat) will be eliminated from the mix as the products evolve. But we will never really know if this made any difference for health outcomes. Nor will we know if any alterable small risk remains — the epidemiology is simply incapable of detecting small risks in a population of ex-smokers. Anyone choosing to vape should recognize this and make their decision based on it. Anyone who is very worried about what they are inhaling should probably just switch to snus or NRT, which are almost certainly slightly lower risk than vaping, rather than fall into the trap of believing that playing whack-a-mole with individual chemicals will change that.

13 responses to “Diacetyl in e-cigarettes — what we can really say (not much)

  1. “But given the complexity of biology it is possible that long-run exposure causes that much risk or even more, particularly for more harmful combinations of liquid chemistry, hardware, and behavior.”

    So, there is a chance that vaping will cause more damage than smoking in the long turn and people will massive dying from vaping 30 years from now?

    • Carl V Phillips

      Well it depends on what you mean “a chance”. It is not full-on impossible in a mathematical sense. On the other hand, we know enough to be quite confident that the chance is so low it is not even worth considering in our practical dealings with the practical world. (Notice the nested quantitative statements there — anyone trying to seriously make a decision, rather than just manufacture doubt, should be thinking in terms of the probability that a particular quantity is the true value, not merely that it might be.) Indeed, the chance that vaping is 20% as harmful as smoking is not even worth considering based on what we know now.

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  4. I wanted to ask, given the much higher concentrations of diacetyl in tobacco cigarettes and given we are told that no smoker has suffered from ‘popcorn lung’, can we read anything into this? Or is it irrelevant?

    • Carl V Phillips

      Yes, we can learn something from it (we can learn something from most anything that relates to the question at hand) just not as much as is often implied by those who see that figure and half-understand it. To the extent that there is more diacetyl in cigarette smoke, and there are no other changes that affect its impact, it further reinforces the claim that this molecule, alone, in vapor causes anything other than a trivial risk of disease. That is something and should be reassuring.

      However, note all the caveats. Is the physical or biochemical impact on the lungs the same? It might or might not be — you have exceeded my expertise there. A particular molecule can have very different effects depending on its micro-environment. It is possible that diacetyl has bad effects but something else in smoke blocks the effect or that smoking alters the lungs in a way that protects against them. It is possible, as I said, that diacetyl is harmful only in the presence of some other chemical(s), which exist in popcorn flavoring. The other chemical(s) might not be in smoke. Might they be in vapor? Probably not, but it is possible.

      The bottom line is that we should definitely be more reassured about the risk from diacetyl being minimal, given that we live in a universe where it can be found in cigarette smoke, and lots of people smoke, and they do not seem to get the disease that is attributed to diacetyl. If we somehow knew nothing else, this observation would assure us that the risk from in in vapor is very likely to be very small. The observation that it is in vapor and vapers do not get the disease is much more reassuring, however, because it is the actual exposure of interest. We definitely should not make the mistake of saying that because of this observation, there is no possible way it can be harmful in vapor.

      Re the caveats about my personal expertise there, it is worth noting that I invited someone with substantially more expertise in those particular sciences to take the interview instead of me or with me. He balked at participating much harder than I did. This is to be expected. For a real scientist, the more expertise you have about something, the less willing you are to make simplistic pronouncements or opine without doing a thorough review of the evidence (which you can understand). My expertise is great enough about the topics, methods, and general area of inquiry that I could make the statements I did with confidence, but was completely unwilling to respond in any way to some of the specific questions that were posed. Someone with more specific expertise would not want to back off to that level, so if he had not done the research to say more, he would want to stay out.

      That is why this particular point, and discussion about e-cigarettes and health in general, is such a hotbed of Dunning-Kruger Syndrome (aka “Mount Stupid” thanks to a great recent cartoon). There is demand for simplistic answers, but real experts refuse to provide those unless they have such a complete understanding that they are willing to distill it into a simplification. But there are lots of people who know enough to say something that sounds like something an expert might say (to someone with no scientific expertise), but are actually so inexpert that they do not even realize they are not expert. Real expertise is so far over the horizon from them that they do not even understand what it would look like.

      • Are there a real scientists who study the effects of a vapor on lungs? I don’t know who to
        believe anymore…

        • Carl V Phillips

          There is no decent epidemiology (the study of what we actually want to know, real effects of the real exposure on real people) despite it being a possibility for looking at acute effects. Thus we have to rely on “there is no apparent outbreak” and “there are no credible reports of a case of…” type analysis. There are various people doing lab studies, but those do not tell us much except in cases where something is massively and obviously harmful (and they still do not quantify any effects).

          A good rule of thumb (though it will not give you any solid answers in this particular case) is pay attention to people with a history of doing good work in a field of analysis. If someone’s entire contribution to lung research is in the context of either anti- or pro-tobacco product advocacy, they are probably not a good choice to trust.

  5. And i have another question… Is there a difference if i inhale vapor mildly, not deeply into the lungs, just to enjoy throat kick and fast exhale through the nose or mouth. I do mouth to lung (throat) inhale.

    • Carl V Phillips

      Mouth puffing rather than inhaling into the lungs reduces the risk from smoking (which is a big reduction because it is a big risk) and presumably would reduce any risk from vaping (which would be a small reduction because it is almost certainly a small risk in the first place). What you describe seems like it is pretty close to this. (Personally I always only mouth puff when I sample any inhaled product.) There is a lot of noise about “inhaling deeply” being worse than inhaling less deeping in the discussions of smoking, though the evidence is rather more tentative than the rhetoric would imply. It would be pure guesswork to try to assess whether the risk to the lung from vaping (if there are any) would be changed by this.

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