E-cigarettes and health — here's what the evidence actually says

Stepping into the health debate around electronic cigarettes is a messy and frustrating exercise. Depending on whom you ask, these devices are either the best technological solution to the smoking pandemic or the biggest looming threat to public health.

So to sort through the research and figure out whether e-cigarettes are actually safe, I read through more than 60 studies, articles, and reviews, and interviewed nine researchers and health experts about their work.

Here's the bottom line: If you're a chronic smoker looking for a nicotine fix and trying to decide between smoking and vaping, most experts would agree there’s a compelling case that e-cigarettes are less harmful.

But a nonsmoker, or an ex-smoker, should think twice before taking up the habit. Even if e-cigarettes are safer than regular cigarettes, that doesn't mean they're totally safe. At this point, we just don't know. There have been no published long-term studies on the health of e-cigarette users, so the impact of vaping on the body over many years or decades is completely unknown. There are about 500 e-cigarette brands and more than 7,000 flavors on the market, and they work in different ways, delivering varying amounts of nicotine, toxins, and carcinogens. This means it’s hard to say anything concrete about the safety and health impact of all devices based on the research we do have.

Many of the studies out there are also limited in scope or flawed and biased by design. Adding to the uncertainty, in as many as one-third of e-cigarette studies, the authors have declared a conflict of interest, raising questions about bias.

This uncertainty has the research community divided. On one side, there are tobacco-control researchers who have spent their entire careers exposing the evils of the tobacco industry and view e-cigarettes in a negative light almost by default. There are also public health researchers who take a "zero-risk" approach and believe that, given the unknowns, these devices should not be tolerated. Many of these folks remember that it took decades for the tobacco industry to admit to the harms smoking caused, and that until very recently it falsely claimed "light" or "mild" cigarettes were a healthy alternative.

On the other side, there are researchers who view e-cigarettes more favorably for their harm-reduction potential. They think these devices could save the lives of millions of people. For now, researchers and industry representatives are either unlikely bedfellows in a harm-reduction game plan or at odds over the best way forward.

What is the state of the science on e-cigarettes?

The state of the science, in short, is crap. Many of the studies don't pass basic tests of methodological rigor. There are only two published randomized control trials — considered the gold standard of scientific evidence — on e-cigarettes (this one and this one). Worse, many of them may be hopelessly corrupted by industry money or bias.

Consider the conclusion of one of the most recent systematic reviews on e-cigarettes (which, unlike some of the others, was not supported by industry funding). This review, published in the American Journal of Preventive Medicine in 2014, looked at 76 of the best available studies on e-cigarettes:

"Due to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of [e-cigarettes]."

The researchers also found that in 26 of the studies reviewed, the authors had declared a conflict of interest. They wrote: "Most studies were funded or otherwise supported/influenced by manufacturers of [e-cigarettes], but several authors had also been consultants for manufacturers of medicinal smoking cessation therapy."

When I asked one of the review's authors, Martin Døssing, what he made of the current evidence base on e-cigarettes, he said, "The literature is very poor." He continued:

"The most worrying aspect of e-cigarettes is that we do not know the long-term health consequences of daily use. Will e-cigarette users come up with unsuspected diseases such as cancers in 10 or 20 years from the start of use 10 years ago? Substances known to be carcinogenic to man have been found in a few brands of e-cigarettes."

One of the great complexities of research in this area is the fact that e-cigarettes types vary so widely. "What is an e-cigarette?" asks Judith Prochaska, a professor at Stanford's prevention research center, rhetorically. The devices can hold a wide range of flavors and chemicals, they burn and deliver nicotine differently, and their technology is advancing fast. It’s hard to know whether findings of studies are generalizable at all.

But perhaps the biggest complication is that e-cigarettes are extremely new — and so the most important research hasn't had time to be conducted. The first peer-reviewed studies only started emerging in 2010, meaning we are still far from the kind of scientific certainty that can give clues about the effects of e-cigarettes over decades.

How do e-cigarettes work?

(Marco Prati/Shutterstock)

These battery-powered devices deliver nicotine to the user through a vapor by heating a solution of propylene glycol or vegetable glycerin, flavoring, and other additives. Flavors range from butter rum to caramel macchiato to strawberry lemonade.

E-cigarettes have become increasingly popular in recent years. In 2015, the Centers for Disease Control and Prevention (CDC)  reported that the use of e-cigarette devices among middle school and high school students tripled between 2013 and 2014. That means about 13 percent of students now use them — outstripping the number who smoke conventional cigarettes. By 2017, sales of e-cigarettes in the US are expected to surpass those of conventional cigarettes, reaching $10 billion. The three major tobacco companies, through their buying up of small e-cigarette companies, could share 75 percent of these profits over the next 10 years.

The major appeal of e-cigarettes is that they don’t contain tobacco and the exhaled vapor carries no harmful smoke, tar, or carbon monoxide. They also seem to have significantly fewer toxins and carcinogens than regular cigarettes.

Key question #1: How dangerous are e-cigarettes?

We don't actually know. As an American Heart Association review on e-cigarettes states: "In general, the health effects of e-cigarettes have not been well studied, and the potential harm incurred by long-term use of these devices remains completely unknown."

Based on the science so far, short-term exposure to e-cigarettes doesn’t appear to carry serious and immediate health effects. As the AHA points out, "The data on health effects to date, studied primarily in healthy people with short-term exposure, reveal little or no evidence of severe adverse events. Respiratory irritation and the bronchial constriction from a propylene glycol aerosol raise concerns about harm to people with asthma and chronic obstructive pulmonary disease, but one small study reports no harm but rather benefit when users quit smoking or smoke fewer cigarettes per day."

Keep in mind, however, that the research here is still early, and this conclusion on e-cigarettes could change once tens of thousands of people — and not just dozens or hundreds — have been studied.

Bigger questions center on the toxicity of e-cigarette’s aerosol and liquids — and their potential long-term effects. Maciej Goniewicz, of Roswell Park Cancer Institute, is one of the leading researchers in this area. In one study, he looked at 12 brands of e-cigarettes and found that their vapors were mostly composed of nicotine and a nicotine solvent (propylene glycol or vegetable glycerin). Also, the levels of toxicants and carcinogens in e-cigarette vapor were nine to 450 times less prevalent than in conventional cigarette smoke.

Though propylene glycol and glycerin are generally considered safe substances, not a lot is known about the long-term effects of daily inhalation, Goniewicz says. There’s some evidence from theater settings — in which propylene glycol has been used to create fog — that suggests it can be a lung irritant. Goniewicz has also found toxic substances and cancer-causing compounds, such as formaldehyde and acetaldehyde, in e-cigarettes.

Reasons for concern have popped up elsewhere — though, again, nothing conclusive yet. Some research has shown that cells exposed to e-cigarette vapor showed similar genetic changes as cells exposed to conventional cigarette smoke — raising concerns that e-cigarettes could potentially lead to lung cancer.

One big problem here: E-cigarette products vary widely, making them tough to study. "Some had a higher presence of the toxicants, while other products have very low levels or even undetectable levels of toxicants," Goniewicz said. What's more, research shows that the heating process in e-cigarettes can change the composition of potentially harmful chemicals. "If the temperature goes too high, then there are more toxicants," he warned.

Chris Bullen, an e-cigarette researcher and professor at the University of Auckland's school of public health, noted that newer electronic cigarettes use a heating control mechanism that prevents "cooking" the e-liquid, and reduces the risk of generating harmful aldehydes. He cautioned about drawing conclusions from older studies that may be based on out-of-date technology. But he also added that there's a lot of inconsistency in manufacturing quality: "Backyard operators" who make e-cigs may run the risk of contamination.

"Then there are the flavors," he added. "Very little is known about what happens with these when heated and inhaled for weeks, months or years."

Key question #2: Are e-cigarettes safer than regular cigarettes?

There are nearly 500 brands and more than 7,000 flavors of e-cigs. (Shutterstock)

Most researchers cautiously lean toward "yes" — despite the unknowns.

Because the immediate harms of e-cigarettes appear to be minimal compared with regular cigarettes, many researchers agree that there’s a compelling case to be made for e-cigarettes as a harm-reduction tool for heavy smokers, at least in the short term. (That was the conclusion of an August 2015 Public Health England review of the evidence, which estimated that e-cigarettes are "95 pecent less harmful" than regular cigarettes.)

The tougher question is how the long-term impacts of e-cigarettes compare to the long-term impacts of smoking. "It’s probably fair to say that a long-term e-cigarette user is not going to die from tobacco-caused disease," says Thomas Eissenberg, co-director of the Center for the Study of Tobacco Products. "But it’s not clear whether they’ll die from an e-cigarette-caused disease and whether their rates of death will be less than, more than, or the same as the rates of death we see from tobacco-caused diseases."

Key question #3: Do e-cigarettes actually help people stop smoking?

So far, two randomized studies (here and here) have looked into the question of quitting — and both found that e-cigarettes may indeed help smokers quit. Another lower-quality web-based survey came to the same conclusion.

But not everyone's convinced. As a systematic review by the Cochrane Library noted: "The small number of trials, low event rates and wide confidence intervals around the estimates mean that our confidence in the result is rated 'low.'" For example, there were weaknesses in the randomized trials. One trial compared e-cigarettes with nicotine patches for helping people quit. But participants had to go out and pick up the patches from the pharmacy, whereas e-cigs were delivered to their doorsteps — a difference that could have biased the results in favor of e-cigarettes.

Other evidence, meanwhile, suggests that e-cigarettes may not be so effective at helping people smoke fewer traditional cigarettes. A study published in JAMA Internal Medicine in 2014 concluded: "E-cigarette use by smokers was not followed by greater quitting, or reduction in consumption one year later." Another 2015 study in the journal Addiction found that daily use of e-cigarettes seemed to be associated with an increase in the rate of attempts to quit smoking and less smoking, though not increased rates of quitting. These were both observational studies, so lower quality than the randomized trials.

So the evidence on quitting is still limited and has mixed results. And there are lots of harder questions that remain unanswered, as the American Thoracic Society has noted. Could e-cigarettes prolong the process of quitting? Could they make quitting less likely? For now, we don't know.

Key question #4: Could e-cigarettes "re-normalize" smoking?

The use of e-cigarettes is growing among adolescents, while conventional cigarettes fall out of favor. (NEJM)

This is another concern some public health researchers have. After years of anti-smoking campaigns, rates of traditional cigarette smoking are falling. But what happens if e-cigarettes become more popular?

Could the availability of e-cigarettes entice former smokers to get hooked on nicotine again? Will e-cigarettes be a "gateway" device that carries people who would never have started smoking cigarettes into nicotine addiction? Or, relatedly: If more and more people use e-cigarettes, could that "re-normalize" regular cigarette use?

Those in favor of e-cigarettes say this renormalization is unlikely. They point to recent CDC data showing that the threefold increase in e-cigarette use among youth has been accompanied by a decline in the use of traditional cigarettes. There's also some research that suggests nonsmokers who try e-cigs don't progress to daily use — that it's not a gateway drug.

"Though we see experimentation," said Lynne Dawkins, an experimental psychologist at the University of East London (who has received research funding from the industry), "we're not seeing evidence of people using them regularly."

On the flip side, researchers less enthusiastic about e-cigarettes note that the absolute use of nicotine products (such as hookah and cigars) has been trending up. There's also this 2015 study in JAMA, which suggests students who use e-cigarettes are later more likely to report smoking combustible cigarettes compared with non-vapers. This observational study couldn't prove that vaping caused the cigarette smoking, but while firm evidence on how e-cigarettes are changing behaviors is lacking, some researchers are concerned.

"Maybe you get a chronic smoker to quit," said Stanford's Prochaska, "but what about this next generation coming up who would not have picked up a combustible cigarette because it’s a dying behavior, but these devices are so trendy and they’re flavored and marketed to be really appealing to kids?"

Key question #5: Is nicotine, on its own, harmful?

(Melanie Tata/Flickr)

Some researchers — especially those who view e-cigarettes more favorably — argue that nicotine in and of itself doesn’t harm people. The problem, they say, is the tobacco and other chemicals in combustible cigarettes.

The more staunch tobacco-control types argue that nicotine itself is dangerous and addictive and that it should be avoided. That puts e-cigarettes in a less favorable light.

The truth likely lies somewhere in between. As one review stated, "Nicotine is the addictive chemical in tobacco smoke, but its involvement in smoking-related harm (outside pregnancy) is very small, if any, compared to cigarette smoking." Another systematic review pointed out that nicotine can have a variety of potential health effects, from raising one's cardiovascular risk to causing birth defects in pregnant women.

There's also some emerging science that suggests nicotine may confer benefits, from helping to treat Parkinson's disease to enhancing attention and focus.

The other nicotine question has to do with whether e-cigs even deliver enough to satisfy smokers. We know from this Cochrane systematic review that if you want to help people quit smoking, you need to give them nicotine. Yet what's clear right now is that not all e-cigarettes deliver the same amount of nicotine.

Some studies, such as this one in Nature, found that the nicotine delivery to the bloodstream from these devices varied, and was still much slower and lower than the concentrations that regular cigarettes give smokers. "Compared to smoking one tobacco cigarette," the researchers wrote, "the [e-cigarette] devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after five minutes of use."

Other more recent studies, like this one from 2015, suggest that at least some e-cigarette users may get nicotine doses similar to those from tobacco cigarettes.

Key question #6: Is secondhand e-cig vapor bad for you?

A comprehensive analysis of the research, published by the American Heart Association, suggests e-cigarette vapor contaminates the air with nicotine and toxins, but the long-term health effects of exposure to these secondhand chemicals remain unknown.

Roswell Park Cancer Institute researchers found e-cigarette vapor leaves nicotine in indoor environments, but they didn't find significant traces of tobacco-based toxins such as carbon monoxide. And conventional cigarettes left 10 times more nicotine than e-cigarettes. But the study, the authors cautioned, looked at a limited number of chemicals.

The researchers at the Roswell Park Cancer Institute found traces of select toxins in e-cigarette vapors, but these various toxins were nine to 450 times less prevalent than in conventional cigarette smoke. Another study from German health researchers also found increased levels of some toxins in the air following e-cigarette use.

So it's still unclear whether consistent exposure to secondhand nicotine and toxins, especially the low levels left by e-cigarettes, could be dangerous to someone's health in the long term.

Meanwhile, secondhand smoking from conventional cigarettes, as the Mayo Clinic explains, is proven to be very bad for people's health.

The answer to the secondhand vapor question could be crucial to public health policy: E-cigarette supporters argue that the public ban on smoking shouldn't apply to e-cigarettes because secondhand vapor isn't proven to be dangerous. Whether that claim holds up in future research could decide if people can legally use e-cigarettes in public settings. For now, the FDA notes the public health standard is clean air.

Do these scientific debates matter for policy?

Yes. Right now, regulators all over the world are trying to figure out how to deal with e-cigarettes.

While some countries have banned the devices outright, the US federal government regulates them.

This is a new development, as of spring 2016. The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration the power to regulate the tobacco industry, but e-cigarettes — along with other tobacco-related merchandise such as cigars and nicotine gels — were left out.

By April 2011, the FDA announced it was going to address this gap. Then in April 2014, the agency proposed a draft rule that will redefine e-cigarettes as "tobacco products." The rule, which became final in 2016, brings e-cigarettes under the Tobacco Control Act. Among other things, the rule will:

• Ban e-cigarette, hookah, pipe tobacco, and cigar sales — either in person or online — to minors (some states have already done this)
• Require age verification by photo ID for purchase of these products
• Require manufacturers of products that hit the market after February 15, 2007, to submit their products for FDA approval — disclosing ingredients, marketing plans, and product designs — within 12 to 24 months depending on the regulatory pathway followed
• Require companies to put health warning labels on e-cigarettes and other tobacco products, including warnings of the possibility of addiction and the health effects of nicotine
• Prohibit selling of covered tobacco products in vending machines (unless in an adult-only facility)
• Ban free samples of e-cigarettes and other tobacco products

Some public health officials and vaping advocates think that regulating e-cigarettes as tobacco products is overkill; after all, the devices don't even hold tobacco. They also worry that if e-cigarettes are regulated too heavily or barred from the market, the public could miss out on a device that could have saved lives.

Some experts also think heavy regulation could halt innovation, deterring manufacturers from creating more advanced devices with better nicotine delivery systems that could help reduce smoking.

As Peter Hajek, a professor at Queen Mary University of London, put it, "Regulators need to watch out for unintended consequences of overzealous regulation, such as stifling such developments or making e-cigarettes more expensive and less attractive to smokers; and also avoid conveying a message that e-cigarettes are regulated as strictly [as] or even more strictly than cigarettes because they are as bad."

FDA officials are conducting a scientific review of e-cigarettes and their effects. Until then, states, counties, and cities have been enacting their own e-cigarette regulations. The American Nonsmokers' Rights Foundation tracks which lower levels of government have acted here.

Further reading:

• Why e-cigarettes are dividing the public health community
• Behind the Vapor

• Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery

• Electronic cigarettes as a method of tobacco control

• Electronic cigarettes for smoking cessation

• Levels of selected carcinogens and toxicants in vapour from electronic cigarettes

• Acute electronic cigarette use: nicotine delivery and subjective effects in regular users

• Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation

• Tobacco Use Among Middle and High School Students