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The Diacetyl Debate: What Top Researchers Have To Say

Diacetyl in E-Juice

It’s hard to have missed the recent furor about diacetyl in e-liquid. The media whipped up a typically exaggerated storm of concern about the buttery flavoring, and familiar battle-lines were drawn among the vaping community: should we be concerned about diacetyl? Should we be putting more pressure on mixers to remove it from their juices? Or is the whole issue being blown out of proportion?

The answers are hard to come by. But it’s an important issue, so in an attempt to get to the bottom of it and explore the issues, we’ve spoken to scientists and some prominent vapers to get their take on the buttery controversy.

There are two parts to the problem – the science, and what we should do about it – so we’ve put together a pair of posts, each addressing one element of the debate. This post gives you the low-down on what the research says about diacetyl, with input from some prominent scientists in the world of vaping, and the companion post talks about the more general, industry-related issues with some well-known vapers.

So what do you need to know about the evidence on diacetyl? What does the research we have so far tell us? We’ve looked through the studies and spoken to Dr. Konstantinos Farsalinos, Dr. Michael Siegel and Dr. Carl V. Phillips about the issues.

What is Diacetyl and Why is It Used in E-Juice?

diacetyl in e liquids

Diacetyl is a yellow-green liquid that has a strong buttery flavor. It’s the simplest form of a group of organic chemicals called diketones: it has two double-bonds of carbon and oxygen, which in the case of diacetyl are located right next to each other. It has the alternative name butane-2,3-dione.

Diacetyl is found naturally in fruits, coffee, honey, dairy and vinegar, as well as being produced in the fermentation process for beer and wine. The buttery flavor it imparts has led to its use as a flavoring chemical in a wide range of products, including microwave popcorn, cooking oil, candy, chocolate, frosting and many other foods.

The delicious flavor – and its presence in many artificial flavoring mixtures – is why it’s also used in e-liquids. If you’re hoping to make an e-juice that has a buttery component to the flavor, diacetyl is one of the only chemicals you can use to make it happen. That’s why the two studies looking into diacetyl in e-juice – both of which looked specifically at sweet flavors – have found that around three-quarters of liquids contain it at detectable levels.

Is Diacetyl Dangerous?

diacetyl testing

Diacetyl is generally recognized as safe by the FDA. But the issue is a little more complicated than that: the “generally recognized as safe” classification says nothing about the risks when inhaled; it’s specifically about the chemical being added to food. When you’re pulling the chemical directly into your lungs, the issue isn’t quite so clear-cut.

When reports of workers exposed to flavoring mixtures developing a rare lung condition began to surface – mainly around the turn of the millennium but as early as the 80s – researchers begun to look into what could be causing the problem. Many of these case reports came from popcorn plants, and workers there were exposed to quite a lot of potentially harmful chemicals. How do you work out what’s going on? How do you tease out the true cause from the multitude of potential ones?

popcorn lungWell, it isn’t easy. The National Institute for Occupational Safety and Health looked into six microwave popcorn plants, and these investigations produced some suggestive results, such as the fact that those exposed to the most diacetyl had the biggest problems with obstructed airways, and those working in the mixing and packaging rooms (who dealt directly with flavorings) were the only ones who developed lung problems.

So the lung problems definitely seemed to have something to do with flavorings. Diacetyl was the most widely used flavoring, but there were still a lot of different flavorings in the air, so it was hard to be sure.

But there is other evidence that suggests that diacetyl was to blame. Animal studies – where mice and rats are exposed to very high quantities of diacetyl – show that the chemical can lead to lung damage in the absence of the 100 or so other chemicals in the air of the popcorn plants’ mixing rooms. When these studies used lower doses, the consequences weren’t as severe, though, and the effects from a mixture of butter flavorings were generally worse than diacetyl alone.

Animal studies are inherently limited, too. We aren’t mice or rats, after all. However, there is also some evidence from plants specifically manufacturing diacetyl, where workers are exposed to much fewer different chemicals but still develop lung problems like those seen in the popcorn plant workers.

We spoke to Dr. Konstantinos Farsalinos, a leading researcher on vaping (and blogger at E-Cigarette Research), who conducted the first study looking for diacetyl in e-liquid about the evidence.

He comments:

What Dr. Farsalinos says about diacetyl in e juice“There is evidence that exposure to diacetyl can lead to respiratory dysfunction. The issue is not so much related to popcorn lung disease (bronchiolitis obliterans), which is a rare condition, but with non-specific respiratory dysfunction. According to the NIOSH draft on diacetyl, people exposed to diacetyl through inhalation have much higher risk of developing respiratory dysfunction compared to the general population.” – Dr. Konstantinos Farsalinos

So it’s not all about “popcorn lung” – it’s more general breathing-related problems we should be concerned about.   

A final indication of the potential for problems from inhaling diacetyl is the story of an ordinary consumer  who loved microwave popcorn so much he ate at least two bags a day for ten years. When the popcorn was ready, he’d open up the bag and inhale the fumes from it (OK, maybe he wasn’t exactly ordinary…).

The 53-year-old Colorado resident started to have lung problems, and his doctor was able to draw the link to diacetyl, despite not knowing about his popcorn habit. Further investigation showed that his home contained diacetyl in levels much like those seen in popcorn factories. Opening a bag of popcorn releases most of the 0.78 mg emitted throughout the preparation process, so he was probably inhaling fairly large amounts.

Is There a Real Risk to Vapers from Diacetyl?

popcorn lung from diacetyl

So there is quite a bit of evidence to suggest that inhaling diacetyl is not a good idea. But the idea of a risk to vapers from diacetyl in e-liquid isn’t so clear-cut. The amount of diacetyl vapers are exposed to is a crucial factor, and at vaping-like exposure levels, there is basically no evidence outside of vaping itself.

We asked Dr. Carl V. Phillips – scientific director of CASAA, ex-Professor of Public Health and active researcher in tobacco harm reduction – about the issue and the potential for risk to vapers. He offered a response which has been published on his blog, Anti-THR Lies (which we’d encourage anybody interested to read in full), which contains a crucial point:

Carl V. Phillips“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.” – Dr. Carl V. Phillips

He discusses some methods for making such “heroic guesses” – one of which is the simple idea that a larger dose produces a larger response – but then cuts to the chase:

Carl V. Phillips“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.” – Dr. Carl V. Phillips

The only question is whether or not we’ve been vaping for long enough to even notice any such outbreaks. The guy who ate too much popcorn was having two bags a day and inhaling fumes for 10 years before developing lung problems, so it could well be that problems arise in vapers in the future. The exposures from vaping are much smaller (generally less than 0.065 mg per day), but could still lead to problems in the long term.

Cigarette Smoke and Diacetyl: What it Means for Vapers

This general uncertainty is why the most recent study about diacetyl raised a lot of concern, in the media and from vapers. However, this result was widely countered with one simple point: cigarette smoke contains much more diacetyl than e-cig vapor.

We spoke to Dr. Michael Siegel, who blogs on vaping and related issues at the Rest of the Story, who agreed that occupational studies suggest a risk from inhaling large amounts of diacetyl, but drew attention to the quantities in smoke:

Michael Siegel“Given the fact that diacetyl levels in e-vapor are about 750 times lower than in tobacco smoke and that smokers themselves do not get popcorn lung, there seems to be no concern about popcorn lung as a risk among vapers. Nevertheless, it is my opinion that diacetyl should not be used as a flavoring.” – Dr. Michael Siegel

As his blog post on the study explains, the 750 times lower figure is based on one day’s worth of vaping vs. one day’s worth of smoking, which he classes as one cartridge per day vs. 20 cigarettes. One cartridge is about 1 ml, so this is something of an underestimate (most vapers consume around 5 ml per day or more), but the overall point does hold: cigarette smoke contains much more diacetyl. So if smokers don’t get popcorn lung, surely vapers won’t either?

It’s a compelling line of reasoning, but it falls flat when examined more closely. We mentioned this argument to Dr. Farsalinos, and he responded:

What Dr. Farsalinos says about diacetyl in e juice“We have addressed this issue in our paper on diacetyl which was published in September 2014. We should not forget that cigarette smoke contains not only diacetyl (at high levels) but also many more respiratory toxins. The combined exposure to these toxins can lead to a different form of respiratory disease, Chronic Obstructive Lung Disease. Also, it is important to stress that Chronic Obstructive Lung Disease is much more common in smokers compared to popcorn lung disease in those exposed to diacetyl in the occupational setting.” – Dr. Konstantinos Farsalinos

So while smokers don’t necessarily get popcorn lung, they do get something quite similar, so the specific argument doesn’t stand up to scrutiny that well. More generally, though, the fact that smoke contains much more diacetyl than vapor does mean that vaping is going to be much safer than smoking in terms of diacetyl exposure.

Dr. Farsalinos adds:

What Dr. Farsalinos says about diacetyl in e juice“On average, the levels detected in our study were by far lower compared to smoking, and the second study found levels even lower than ours. We cannot exclude the possibility that there may be some liquids with high levels of diacetyl. That is why, I strongly support the need for the industry to test all liquids for the presence of diacetyl and related chemicals, and make every effort to remove these chemicals through reformulating the liquids. I consider exposure to diacetyl through e-cigarettes as an unnecessary and avoidable risk; however, in most cases, the risk is by far lower compared to smoking.” – Dr. Konstantinos Farsalinos

Workplace Exposure Limits for Diacetyl – What Do They Mean for Vapers?

Diacetyl Limits

So, despite a lot of uncertainty about the overall risks, it’s safe to say that the risk from vaping is much smaller than that from smoking. To estimate the overall risks, though, as Carl V. Phillips argues, would involve assuming too much based on very limited data, especially at vaping-like amounts.

There is a potentially useful guideline for vapers in the form of the occupational exposure limits set for diacetyl. But there is some disagreement about the usefulness of this, as Dr. Farsalinos explains:

What Dr. Farsalinos says about diacetyl in e juice“Some scientists are against the use of occupational setting limits because they refer to the working population and not the general population which may include vulnerable people. However, I think this is not valid because e-cigarettes are used by smokers, who are exposed to a much higher health risk from smoking compared to the general population of non-smokers. Thus, the occupational setting limits can be a valuable guide in a risk assessment analysis.” – Dr. Konstantinos Farsalinos

NIOSH has set a recommended maximum for the average diacetyl content of the air of 5 parts per billion, which equates to about 65 micrograms a day. This was calculated as part of Dr. Farsalinos’ study on diacetyl in e-liquid, which found that the average exposure for a vaper would be below this threshold. The newer study found even lower levels.  

Dr. Farsalinos continues:

What Dr. Farsalinos says about diacetyl in e juice“We should not forget a basic principle in toxicology, that the dose determines the toxicity. Detectable but extremely low levels are highly unlikely to cause any harm. The NIOSH safety limits are associated with less than 1 in 1000 chances of developing non-specific respiratory obstruction after exposure to diacetyl for 45 years. This risk is absolutely minimal compared to the smokers’ risk of developing lung disease. I should also note that the European Union has set safety limits for diacetyl which are much higher than what NIOSH has determined.” – Dr. Konstantinos Farsalinos

Although many juices will exceed these levels, as well as the fact that occupational limits assume two days unexposed each week, it’s clear that the risks to vapers, if they do exist, are probably fairly small.

Acetyl Propionyl and Acetoin: Are the Risks Any Different?

Acetyl propionyl (2,3-pentanedione) is the main alternative to diacetyl in use in various industries, in response to the concerns raised about diacetyl. The problem is that this is another diketone, and it’s structurally very similar to diacetyl (which is why it can replicate the flavor), so the effects would probably be similar too. There isn’t direct evidence of risks to humans from inhalation, but the results from animal studies suggest that the damage to the lungs is virtually the same.

Dr. Farsalinos responded in line with this evidence:

What Dr. Farsalinos says about diacetyl in e juice“We have some evidence that acetyl propionyl may be similarly harmful to diacetyl. Thus, it should not be used as a substitute for diacetyl.” – Dr. Konstantinos Farsalinos

For acetoin (another potential alternative), the picture is a lot less clear. He continues:

“As for acetoin, there is no convincing evidence that it is harmful. However, diacetyl is a byproduct in the production process of acetoin, and many acetoin samples are contaminated with diacetyl. This may result in the detection of diacetyl in liquids despite reassurance from the manufacturers that they did not intentionally add diacetyl to the liquids.” – Dr. Konstantinos Farsalinos

So, Should We Be Worried?

Ultimately, the title of Carl V. Phillips’ post on diacetyl gets the overall picture across quite succinctly: “Diacetyl in e-cigarettes — what we can really say (not much)”

This might not be the sort of answer you were hoping for (it certainly wasn’t for me), but it’s the cold hard truth. In the post, Phillips writes “though the ‘we just don’t know anything!’ rhetoric we have to deal with is clearly absurd, there is genuine uncertainty.”

We have some potentially useful indications – the much higher levels of diacetyl in smoke and the workplace exposure limits – but these don’t give us too much other than a rough guess. The comparison with smoke is the most comforting for most vapers, but if you’re worried about absolute risk, then the picture is very muddy, to say the least.

Based on what we do know, vaping diacetyl-containing juices does appear to be a bad idea, it’s just in no way clear how much of a bad idea.

However, if you’re concerned, Michael Siegel’s parting advice is really the best take-away message:

Michael Siegel - Debate on Diacetyl “The most important piece of advice for vapers is to remember that vaping is much, much safer than smoking. Any concerns about potential risks of vaping need to be viewed in comparison to the extreme and known health risks associated with smoking. Vapers who are concerned about the risks of e-cigarettes should try to make efforts to eventually get off of e-cigarettes, but by no means should they return to cigarette smoking.” – Dr. Michael Siegel

We’d like to thank Dr. Farsalinos, Dr. Siegel and Dr. Phillips for offering their thoughts and expertise on this issue and making this post possible.

Lee Johnson is a writer and vaper from the UK. He started vaping in 2012, and since then has contributed to E-Cigarette Reviewed, E-Cigarette Direct’s Ashtray Blog and Vaping360. He strongly believes smokers need accurate information about vaping and other reduced-harm alternatives to smoking. He has a degree in physics from the Open University and a passion for all forms of science.

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