Electronic cigarettes – what is science saying as of today?

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 are electronic cigarettes?

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. The respected David Gorski 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 frequently to end content disputes between the pro-Big Vaper and the pro-science sides. 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 one of the reasons why Wikipedia can have a marginal reputation for reliability, but that’s another story.

 

Electronic cigarettes – aldehydes

An article just published in the New England Journal of Medicine, by Jensen et al., could 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 Jensen et al. 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 – dose makes the poison. 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 possibly 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.

In addition, there is some preliminary evidence that the flavoring compounds in electronic cigarettes may be linked to significant damage to lungs.

However, a prominent anti-tobacco public health researcher, Dr. Michael Siegel, believes that electronic cigarettes have a substantially lower amount the diacetyl compound that causes lung damage than in real cigarettes. He also published a letter in NEJM criticizing Jensen’s research here. Although Siegel criticized this research, he also has argued that diacetyls, at any level, should be removed from electronic cigarettes.

One last point that is important in reviewing the Jensen et al. study in the NEJM. As I’ve written before, in the hierarchy of medical research, primary studies, especially ones that have not been repeated, are of a lower rank than other, more powerful studies. There are only five studies that cite Jensen et al., although, to be fair, it has only been two years since publication.

One of the cited articles, by Ogunwale et al., published in ACS Omega, a new but respected journal from the American Chemical Society. Ogunwale et al. examined the level of aldehydes, acetaldehyde, formaldehyde, and acrolein, in the smoke of the vapors from electronic cigarettes. What they found is troublesome,

These aldehydes were detected in the aerosols of all e-cigarettes. Newer-generation e-cigarette devices generated more aldehydes than the first-generation e-cigarettes because of higher battery power output. Formaldehyde-hemiacetal was detected in the aerosols generated from some e-liquids using the newer e-cigarette devices at a battery power output of 11.7 W and above. The emission of these aldehydes from all e-cigarettes, especially higher levels of aldehydes from the newer-generation e-cigarette devices, indicates the risk of using e-cigarettes.

I know, the pro-vaping community is going to be up in arms about the results from both of these studies. They’re going to claim that they use a better vaping liquid. Or the power is too high. Or this or that. And some of those criticisms are valid to an extent. The problem is that the dose response for aerosol aldehydes begins to show an effect at fairly low levels. The only safe vaping liquid is one that never creates aldehydes.

Well, except there is more.

 

Electronic cigarettes – inhaling stuff

These studies above 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, including clinical trials or case control epidemiological studies, either of which may lead us to understand whether these compounds in the electronic cigarettes actually lead to cancer.

One of the criticisms 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 compound may not actually cause a cancer until decades in the future. 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.

But what these studies have established are a biologically plausible reason to consider that vaping is harmful to one’s long term health. That is, there are components of the vaping mixture that could lead to cancer and other lung diseases. We know the components can lead to cancer, but what we don’t know is the dose-response of vaping – that is at what does of vaping can lead to a harmful result. One a day? Two a day? 100?

A recent review article by Chun et al., published in the high impact factor American Journal of Physiology, Lung Cellular and Molecular Physiology, reviewed all the potential compounds from electronic cigarettes that could lead to lung damage and other physiological issues. Here is a partial list:

  • Metals, such as nickel, chromium, aluminum, iron, silver, tin, copper and others can either leach into the vape liquid or be atomized by the electronic spark. Some of these metals have been detected in e-cig vaping liquid. Many of these metals, even at the low levels shown in vaping, can lead to serious lung damage. Some of these metals, like chromium, are actually highly carcinogenic.
  • Nicotine levels is electronic cigarettes are quite high. A regular tobacco cigarette delivers about 2 mg of nicotine to the smoker. However, an electronic cigarette’s liquid generally contains between 12-100 mg/ml of nicotine. So just 1 ml (usually the lower end of what is consumed) can deliver between 6-20X more nicotine to the user. In fact, the LD50 of nicotine is around 60 mg for an average sized adult. If you smoke 2 or 3 ml of a higher concentration vaping liquid, you could do serious harm.
  • Chun et al. criticized the lack of quality control in electronic cigarette liquids in that many had inaccurate or incompletely ingredients lists, which would make it difficult to ascertain toxicity of the liquid when vaped.
  • The researchers also reviewed studies that examined the effects of e-cigarette liquids, either aerosolized or through a vaping, in various models, With the caveat that most animal and cell studies do not end up providing us with clinical significance, all of the studies showed moderate to serious damage after vaping. Although not absolutely convincing in humans as of this time, that’s a lot of preliminary data that is troubling.

Chun et al. concluded that:

In summary, there is a rapidly growing body of evidence derived from in vitro, animal, and human studies that e-cigarette use may have significant pulmonary toxicity. However, many more studies are needed to examine the multiple variables involved in e-cig use, including the role of nicotine, added flavorings, the physics of aerosolization, and the impact of chronic, repetitive exposure. Similarly, there is a compelling need to evaluate toxicity in more clinically relevant model systems, including primary culture of airway and alveolar epithelium, as well as in vivo animal models that combine e-cig exposure with clinically relevant bacterial and viral infections.

 

Other concerns about electronic cigarettes

If there actually was evidence that vaping is a great way to stop real tobacco smoking, that could 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 Centers for Disease Control and Prevention,

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.

One last thing. There is evidence that vaping is dangerous to the fetus in pregnant women. A recent study finds that the high levels of nicotine can be harmful to the developing fetus. In fact, they state that, “we conclude that no amount of nicotine is known to be safe during pregnancy, and studies specifically addressing this risk are crucial and an imminent public health issue.”

 

Electronic cigarette dangers – TL;DR

Here’s what we know now. Electronic cigarettes can 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.

We also know that there electronic cigarette flavorings that contain a compound, diacetyl, which can damage lung tissue. And we also know that vaping causes aerosolization  of numerous metals that have a profoundly negative physiological effect on lung tissue. Finally, a review of vaping on epithelial tissues of the mouth, trachea and alveoli have consistently shown negative effects on those tissues. Although we haven’t produced clinical studies that confirm this preliminary research, that is a lot of convincing evidence that leads us to the strong biological plausibility that there is a causal link between vaping and some forms of lung disease.

If this risk of disease caused by these compounds in electronic cigarettes are borne out by further biological research over the next months or years, then it might lead us to conclude that if you need your nicotine fix, it is much safer to go with a real pharmaceutical like patches or gum.

There is also an argument to be made that electronic cigarettes are a safer alternative to tobacco cigarettes, so they are actually a good way to reduce addition. However, with the higher levels of nicotine along with a raft of lung-endangering chemicals, that argument falls flat. There might be better methods to reduce the addiction to tobacco.

The preliminary research right now is making it clear that vaping could become a public health concern, not unlike what we saw with cigarettes. It’s ironic that the pushback regarding the dangers of electronic cigarettes parallels what we saw with the tobacco cigarettes. First, we saw preliminary data in animals and lung studies. Push back from Big Tobacco, “but those aren’t humans.” Then, we got direct epidemiological data that it was dangerous. More pushback. Unfortunately hundreds of thousands of people die from tobacco every year. Let’s hope that we don’t see the same long-term data from vaping.

 

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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!