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April 16th, 2015:


Over the past few years, electronic cigarettes (often called a personal vaporizer, e-cigarette, or many other trendy descriptions–I’ll abbreviate them as EC, just to save space) have become a popular alternative to tobacco cigarettes. They originally were developed as a tool to quit cigarette smoking, which is factually linked to lung cancer and other respiratory diseases.

However, ECs have become much more than a tool to end smoking, but they have evolved into popular subculture phenomenon known as the “vaping community” that, in many respects, seem to mimic the marijuana advocates. The vaping community continues to push a belief that ECs are safer than traditional cigarettes, have little health risk to the vaper (electronic cigarette smoker), and is much more socially acceptable than smoking cigarettes or cigars.

One of the most ironic and amusing stories about ECs is that Jenny McCarthy, the antivaccination expert who thinks that all ingredients in vaccines are dangerous, has become an advocate for vaping. I bought a brand new, upgraded version 4.7, nuclear powered irony meter, and it just broke. It’s possible Jenny caused a nuclear accident in my house.

What are the dangers of electronic cigarettes? Are there any at all?

What is an electronic cigarette?

Typically, electronic cigarettes use a battery powered vaporizer to aerosolize a liquid that are generally solutions of propylene glycol (a relatively safe diol), glycerol (a commonly used and very safe food and pharmaceutical additive), or both, plus nicotine and flavorant chemicals. The nicotine is usually considered the addictive compound in cigarettes, and the nicotine in the EC is isolated and purified from tobacco plants, so it’s the same one as in any tobacco based smoking product.

The aerosol is inhaled, like a typical cigarette, so the original hypothesis is that it would help wean a smoker from cigarettes by giving them the flavor, nicotine, and inhaling action of a real cigarette, but in a form that many believe is safer than a cigarette. So even if the smoker became addicted to the EC, it was assumed that it was a lot less dangerous than smoking a cigarette. From a financial standpoint, the electronic smoking manufacturers probably would love to get cigarette smokers to become addicted to their device, moving the profits from Big Tobacco to Big Vaper.

Safety of electronic cigarettes?

Ironically (and now my irony meter is broken, so I can’t tell you how ironic this is), the “wars” over the dangers of electronic cigarettes kind of reminds me of the original wars over the safety of tobacco cigarettes. Everyone has an “opinion,” while real scientific research is completely ignored by the side pushing the item. And meanwhile, many communities have not banned public use of ECs, so you might be in a restaurant somewhere, and a guest in the next table will fire up their EC, and you get to inhale the aerosol concoction.

The respiratory tract, including the mouth, throat, trachea and lungs, are extraordinarily sensitive to compounds in aerosol form that can get deep into the lungs, mostly because the cellular linings of these organs are made up of cells that divide frequently and are exposed directly to airborne contaminants. Cigarette smoke, industrial pollutants, asbestos particles, and many other things can be easily inhaled, then cause damage to the lung, many times in the form of cancer.

Even though the lung is sensitive to pollutants, most aerosol liquids aren’t going to do much harm. You can stand in a pine forest, inhale deeply, and there’s probably not much damage going to happen. You can smell a rose, or a freshly baked cake, and you’re going to be fine.

Even oncologists have published articles that seem to indicate there are a lot of unknowns about ECs, and concluded that:

In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation.

These expert oncologists, who specialize in treating mouth and throat cancers, know that the evidence one way or another aren’t in, but in a form of a precautionary principle, suggest that ECs should be avoided. But otherwise, the data seems weak. Orac editorialized about the quality of science behind the safety or dangers of EC’s

I perused PubMed for data on e-cigarette safety, and I was appalled at the crappy quality of the studies out there. For instance, here are two more recent surveys compared to the review article I cited above. They tell us little or nothing more. Even surveys reporting adverse events are not particularly helpful.

This Internet forum survey, for instance, has a built-in selection bias. Even though it tells us that there are a wide variety of reported effects from e-cigarettes, including cough, headache, panic, nausea, tremor, fatigue, reflux, throat and mouth irritation, burning, dermatitis, and elevated blood pressure, it’s hard to tell what the true prevalence of such reported symptoms are.

Not surprisingly, given the uncontrolled nature of these studies, they showed that smokers generally liked e-cigarettes, think they help them decrease or quit smoking, and don’t cause any significant problems. It’s simply amazing how little hard data there are published.

Even more annoying is that the FDA regulates nicotine patches (and other forms of nicotine drug delivery), some of which require prescriptions from MD’s. Oddly, electronic cigarettes, which are, in fact, drug delivery systems, delivering a regulated drug, nicotine, are not subject to FDA control, at least as of today. As long as the electronic cigarette is not marketed with a therapeutic purpose, it is unregulated. That is a loophole 100 km wide, which has inspired a cottage industry in vaping.

Using Wikipedia as a cultural indicator of disputes between real science and those pushing their beliefs, the Electronic Cigarette article has been frozen to end content disputes. Since I’ve been involved with these types of articles in the past, it’s frustrating but humorous. And I don’t doubt that a few of the editors are employees of Big Vaper, trying to push their agenda. Of course, this is why Wikipedia remains a terrible source for anything important.

So is there any research at all about the safety?

Well, an article just published in the New England Journal of Medicine should move the discussion from a fallacious precautionary principle to a serious concern about the the safety of ECs. Using nuclear magnetic resonance (NMR) spectroscopy, a powerful tool used by biochemists to identify small concentrations of organic molecules, the researchers looked not at the pre-aerosolized liquid, which seems to contain safe compounds, but at the aerosol itself after vaping.

What they found may substantially increase concerns about the safety of vaping. The propylene glycol, which is in the pre-vaping liquid, breaks down, over time, into formaldehyde. The reaction between the electronic aerosolizer, propylene glycol, glycerol and formaldehyde creates a “formaldehyde releasing agent,” called formaldehyde hemiacetals, which are known as industrial biocides. Not good, even at the small levels within an EC aerosol.

Formaldehyde itself, in small amounts, is not dangerous. One’s own body creates formaldehyde as a byproduct of numerous biochemical reactions. Many foods contain lots of formaldehyde. But at those levels, it’s far below the dose implicated in any health risk.

But at higher levels, formaldehyde is strongly associated with certain cancers. It is considered a Group 1 compound, carcinogenic to humans, by the International Agency for Research on Cancer (pdf), making it one of the 114 compounds that are known carcinogens. And remember, this formaldehyde is heading to one of the most environmentally sensitive organs in the body, the lungs, mouth, throat, etc.

The researchers found that an e-cigarette user vaping at a rate of 3 ml per day (an average) would inhale 14.4±3.3 mg of formaldehyde per day in formaldehyde-releasing agents. In toxicology, it’s not the presence of something like formaldehyde that matters, it’s the actual dose. And this is where it gets interesting.

So, what does 14.4 mg mean to one’s health. Well, an average pack of tobacco cigarettes (20 of them) would deliver 3 mg of formaldehyde to the smoker. In effect, the EC smoker is inhaling nearly 5 packs of cigarettes worth of formaldehyde.

Now to be fair, tobacco based cigarettes have more than just formaldehyde as carcinogens. But how dangerous is 14.4 mg of formaldehyde?

The researchers calculated the increased lifetime risk of cancer for a tobacco cigarette who smoked one pack per day to be about 900 out of a million, meaning if you took a population of 1 million people, smoking cigarettes would mean 900 more people would contract cancer than the same population with no smokers.

Based on the level of 14.4 mg of formaldehyde, a known carcinogen, it would be estimated that inhaling 3 ml of electronic cigarette liquid in aerosol form would lead to a lifetime risk of cancer 4200 out of a million, nearly 5X larger risk than smoking cigarettes. The cancer risk might be substantially higher because of the type and nature of the form of formaldehyde created by the vaping process.

This moves the conversation from “we don’t know, but it’s probably safe” to “you’re inhaling some carcinogenic compounds that significantly increase your risk of cancer.” The burden of proof should begin shifting to the pushers of these things to show it’s safe over a long period of time. Moreover, it’s clear that the FDA needs to step in and regulate these products like cigarettes, meaning broad warnings of potential risks.


This is one study by one group that have uncovered the level of formaldehyde and formaldehyde hemiacetals in the aerosols of electronic cigarettes. Before there is a consensus of medical science about these products, we’ll need a lot more data from a lot of different sources.

One criticism that the pro-vaping crowd will make is that this isn’t an actual clinical trial showing this dose of electronic cigarettes actually case X number of cancer cases. Unfortunately that takes time, because the cancer causing event may not cause a cancer until decades down the road. It took a lot of time for scientists to identify that cigarette smoking caused cancer, but after years of smokers and better diagnostic tools, by the late 1940’s, researchers could clearly identify the causal link between cigarettes and lung cancer.

Now, a lot of people are doing the typical thing when an article comes out. Pick on this. Pick on that. But like I said recently, only 1 in 100 published articles actually lead clinical importance in health. That’s 1%. Maybe this article contains the initial observations that show us that vaping is dangerous. Or not (and just because 1 in 100 studies are useful, that’s not a predictor, unless you like misusing statistics).

It indicates a potential concern. There should be more and better research, unless you’re in complete denial. And I’m not.

Children, teens and vaping

If there actually was evidence that vaping is a great way to stop real tobacco smoking, that would be a very convincing argument that vaping has some value to the world, far beyond its risks. It’s interesting that Big Tobacco (a group that really tries to harm people) is fighting electronic cigarettes with all the passion that they fight the CDC and FDA.

But like Big Tobacco, Big Vaping (it’s starting to be a thing) is trying, either passively or actively, to create a whole new market with children and teens. According to the New York Times,

…use of the devices among middle- and high school students tripled from 2013 to 2014, according to federal data released on Thursday, bringing the share of high school students who use them to 13 percent — more than smoke traditional cigarettes. The sharp rise, together with a substantial increase in the use of hookah pipes, led to 400,000 additional young people using a tobacco product in 2014, the first increase in years, though researchers pointed out it fell within the margin of error. About a quarter of all high school students and 8 percent of middle school students — 4.6 million young people altogether — used tobacco in some form last year.
Now, I’m not going to moralize what is good or bad about vaping. Cigarette smoking may be a moral issue for some, but for me it’s a health care issue. The same with vaping, and there are some serious health care problems with children and teens’ using electronic cigarettes.

According to Dr. Thomas R Frieden of the CDC,

We want parents to know that nicotine is dangerous for kids at any age, whether it’s an e-cigarette, hookah, cigarette or cigar. Adolescence is a critical time for brain development. Nicotine exposure at a young age may cause lasting harm to brain development, promote addiction, and lead to sustained tobacco use.
The CDC and other anti-tobacco advocates are extremely troubled by the CDC report. They warned that e-cigarettes were undoing years of progress among the country’s most vulnerable citizens by making the act of puffing on a tobacco product normal again, and by introducing nicotine, an addictive substance, to a broad population of teenagers.

Dr. Frieden continued,

…this is a really bad thing. This is another generation being hooked by the tobacco industry. It makes me angry.
I don’t really care if adults risk their lives with vaping (other than trying to quit cigarettes). That’s on them. But getting a child or teen addicted to nicotine and the act of smoking? That’s on the industry. We need to regulating vaping in the same way as smoking–no advertising, strong warnings, strict age laws for purchase, no vaping in any public areas. In essence, restricting vaping as harshly as we do cigarettes.

Here’s what we know now. Electronic cigarettes create a very carcinogenic compound, formaldehyde, which is causally related to increased risks of cancer. Furthermore, we know that the amount of formaldehyde and formaldehyde compounds that are in ECs possibly can be related to a potential 500% increase in cancer than may be caused by formaldehyde in cigarettes, which could be data that supports the dangers of electronic cigarettes.

If this risk is borne out by further chemical and biological research over the next months or years, then if you need your nicotine, either go with a real pharmaceutical like patches or gum, or back to cigarettes. They may be safer (and another irony meter is busted).

With this data, we need to move away from the precautionary principle, that is, we’re not sure it’s safe or unsafe, but until they prove it safe, don’t use it. I hate the precautionary principle, because it is a form of the Nirvana Fallacy, that is if you can’t prove something is perfect, then it’s bad, a fallacy loved by the anti-GMO crowd. But with this data, we move from a fallacy, to data about an inhaled carcinogen produced in rather alarming quantities by these electronic cigarettes. And don’t trust data from Big Vaper–they’re reading from the Big Tobacco playbook.

And let’s regulate this addictive method out of reach or use of children. Period.

One last thing. Those of us who don’t smoke nor think that vaping is wise may find this data troubling with respect to second-hand smoke or vapor. I rarely encounter cigarette smoke any more–it’s generally banned anywhere except maybe in your car.

But I’ve been noticing people vaping publicly. I used to throw water on cigarettes of chain smoking idiots at the next table in a restaurant (way before laws caught up with the science on second hand smoke). I suspect water will have the same effect on the electronics of these things. Oh wait, my city banned it everywhere cigarettes are banned. Yes!!!

Key citations:

· Harrell PT, Simmons VN, Correa JB, Padhya TA, Brandon TH. Electronic nicotine delivery systems (“e-cigarettes”): review of safety and smoking cessation efficacy. Otolaryngol Head Neck Surg. 2014 Sep;151(3):381-93. doi: 10.1177/0194599814536847. Epub 2014 Jun 4. Review. PubMed PMID: 24898072.
· Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in E-cigarette aerosols. NEJM 2015 Jan;372(4):392-3. doi:10.1056/NEJMc1413069.

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