E-cigarettes are increasingly being used as a nicotine alternative as smokers seek ways to kick their habit. They work by heating a pure liquid called e-juice -- composed of flavorings, propylene glycol, glycerin and often nicotine -- until it vaporizes. The resulting vapor is much less offensive to many, both smokers and non-smokers.
But their use has been surrounded by debate, focusing on the lack of evidence regarding the harms associated with their long-term use, as well as their potential to act as a gateway into smoking among teens.
The latest salvo: A study published Monday in the journal Pediatrics found five cancer-causing toxins in the urine of 16-year-olds who inhaled e-cigarette vapor, and a second study found, yet again, that e-cigarettes encourage teens to begin smoking traditional cigarettes.
Last week, a study of nearly 70,000 people found that daily e-cigarette use can double the risk for heart attack. If the user continues to smoke regular cigarettes each day along with e-cigarettes, the combined risk goes up five times.
"E-cigarettes are widely promoted as a smoking cessation aid, but for most people, they actually make it harder to quit smoking, so most people end up as so-called 'dual users' who keep smoking while using e-cigarettes," said Stanton Glantz, lead author of the latter study, in a statement.
Science and public policy have bounced back and forth for over a decade, as different studies produce different -- and sometimes contradictory -- results. Let's take a look at the debate over the years:
Three pack-a-day smoker Hon Lik, a 52-year-old Beijing pharmacist, created the first successful electronic cigarette after his father, another heavy smoker, died of lung cancer. By 2007, e-cigarettes were marketed in Europe and the United States by manufacturer Ruyan as a way to safely stop smoking tobacco.
Hon was not the first person on record to have the idea for an electronic non-tobacco option. Herbert A. Gilbert filed for a patent in 1963, in an era when tobacco smoking was widely accepted and the health risks were less apparent.
In September 2008, the World Health Organization announced that marketers should immediately remove any claims that e-cigs are a "safe and effective smoking cessation aid" because there is "no scientific evidence to confirm the product's safety and efficacy."
Soon after, a study funded by e-cigarette manufacturer Ruyan declared the product to be 100 to 1,000 times less dangerous than smoking tobacco, adding that when using its device, nicotine is "apparently not absorbed from the lung, but from the upper airways."
In May 2009, the Food and Drug Administration released the results of a test of two U.S. e-cig brands, NJOY and Smoking Everywhere, that found "very low" amounts of nicotine in cartridges labeled as nicotine-free. In July, an FDA news release discouraged the use of e-cigarettes, saying they contain carcinogens and an ingredient used in antifreeze, diethylene glycol.
Another concern of the FDA's: E-cigarettes are often marketed and sold to youngsters who, intrigued by the many flavors such as chocolate, bubble gum and mint, might easily adopt a smoking habit as a result of trying the devices.
Vape supporters counter that diethylene glycol was found at a very low, nontoxic level of 1% and that the carcinogens are at the same levels as other FDA-approved nicotine cessation products, like patches and gum.
By the end of the year, Amazon and Paypal restricted the sale of e-cigs on their websites.
Science began to ramp up studies on the topic. Several studies found that interest in e-cigarettes was high among the American public: Google searches for e-cigs were higher in the US than any other nation.
A questionnaire of 3,500 e-cigarette users found that most vaped because they though it less toxic and cheaper than tobacco, and would help them quit or cut down on tobacco smoking. Most ex-smokers (79%) in the study were afraid they would relapse if they stopped using e-cigarettes. The study didn't examine the safety of the product.
Another, much smaller email study of 216 e-cigarette users found that 31% were tobacco-free at six months, and 66% were able to cut back on the number of conventional cigarettes they smoked. A still smaller study of 40 smokers also found that adding e-cigarettes helped smokers reduce the number of traditional cigarettes they smoked each day.
The US Centers for Disease Control announced that e-cigarette use among middle and high school students doubled between 2011 and 2012, mirroring a similar increase in adult use. Most alarming for policy makers: CDC concerns that vaping among adolescents may serve as a gateway to tobacco use.
To measure nicotine delivery, United Kingdom researchers tested 16 e-cigarettes with an automatic smoking machine and found wide variations in nicotine levels per puff, ranging from 0.5 to 15.4 milligrams. In contrast, the typical level from a tobacco puff ranges from 1.54 to 2.60. The wide variation between e-cigarette brands led researchers to question how well they can function as a nicotine replacement device.
Several 2013 publications showed minimal evidence that e-cigarettes help smokers quit. A cross-sectional study of 1,836 tobacco smokers found a significant association with e-cig use and "unsuccessful quitter" status but none with "quitter" status.
Another study of callers to state tobacco quitlines found e-cigarette users significantly less likely to be tobacco-free seven months after they first tried vaping, compared with participants who never tried e-cigarettes.
A New Zealand Health Research Council study of 657 smokers found e-cigarettes modestly effective in helping smokers quit. Interestingly enough, it didn't seem to matter whether they contained nicotine. But the results were similar to FDA-approved nicotine patches.
Some researchers worried that e-cigarette use might distract smokers from proven safe and effective methods for kicking their tobacco habit. "It's filter tipped, low tar, déjà vu all over again," Dr. Frank Leone and Dr. Ivor Douglas wrote in their essay "The Emergence of E-Cigarettes: A Triumph of Wishful Thinking over Science."
The CDC released data showing that the number of calls about nicotine e-juice to poison centers rose from a scant one call per month in 2010 to 215 calls per month in 2014. More than half of the calls involved children under the age of 5 ingesting, inhaling or getting the substance in their eyes or on the skin.
A study of over 75,000 Korean adolescents found e-cigarette use to be strongly associated with current and heavy traditional cigarette smoking. Data from the CDC found that the use of e-cigarettes among US high school students grew from 4.5% in 2013 to 13% in 2014. In that same period, use grew among middle-schoolers from 1% to 4%.
A study comparing the e-cigarette inhaler to the barely used FDA approved nicotine inhaler for smoking cessation found the e-cig version a clear winner with users, providing more satisfaction and a better image.
In regard to safety, a study found that e-cigarettes contain tobacco-specific nitrosamines and heavy metals like cadmium, nickel and lead but that the levels were nine to 450 times lower than traditional cigarettes. The effect on lung function of glycol derivatives found in e-cigarettes was also much less than conventional cigarettes.
Still, researchers weren't convinced. "Although these data suggest that e-cigarettes may be a safer alternative to conventional cigarettes," reviewers Bradley Drummond and Donna Upson said, "there are no data regarding the long-term cancer risk associated with low-level exposure to the detected carcinogens. Similar to cancer risk, there are no published data describing the long-term lung function or cardiovascular effects of e-cigarettes."
A New England Journal of Medicine study set off alarm bells by reporting that some e-cigarettes release formaldehyde, a probable carcinogen, when heated by high-voltage batteries.
A Cleveland Clinic clinical review restated ongoing concerns about propylene glycol and the various food flavorings that are part of e-juice. Though it's considered safe to eat in food in small quantities, researchers say propylene glycol has not been studied when "inhaled deeply and repeatedly."
Another study looked at 51 of the nearly 7,000 e-cigarette flavors currently marketed to check for a flavoring chemical called diacetyl that has been shown to be associated with a disease called popcorn lung. The study found diacetyl at higher than laboratory normal levels in 39 of the tested flavors. Researchers called for "urgent action" to evaluate the "potentially widespread exposure."
In September, new research from the prestigious medical journal BMJ found that teens who used e-cigarettes were more than three times as likely to be smoking traditional cigarettes a year later.
In December, a San Diego Veterans Affairs lab investigation found that two e-cigarette products damaged cells in ways that could lead to cancer, even when nicotine-free. Creating an extract from e-cig vapor, the researchers exposed cells in Petri dishes. The exposed cells showed breaks in DNA strands, which can lead to cancer, and a greater tendency toward cell death.
However, a 2015 report by Public Health England encouraged the medical licensing of e-cigarettes in the UK as nicotine replacement therapy, stating that the use of vaping is "95% safer than smoking" and "can help people to quit smoking and reduce their cigarette consumption" even "among those not intending to quit and rejecting other support."
And research from France's Health Barometer, which conducted telephone interviews with over 15,000 people, found that e-cigs "could have helped several hundreds of thousands" quit smoking, at least temporarily.
In late January, BMJ published a study that quizzed more than 2,000 Hawaiian ninth- and 10th-graders about their e-cigarette and traditional cigarette use, then followed up a year later. Nearly all of the teens (98%) knew about vaping, and 68% considered e-cigarettes to be healthier than smoking.
They found that vapers were more than three times as likely to have begun smoking cigarettes by the next year compared with "never smokers." The study also found that the effect of e-cigarettes was independent of other factors that encourage teens to pick up the habit, such as rebelliousness and lack of parental support.
Though the study showed that any level of vaping led to some cigarette use, it was the heavy vapers who were more likely to become regular cigarette smokers.
In mid-June, the CDC released data about e-cigarette use among working adults, showing that about 5.5 million Americans use the devices but also tend to continue to smoke conventional tobacco products. Over 16% were still smoking cigarettes, 15% used other types of combustible tobacco, and nearly 10% used snuff or other smokeless tobacco.
On the same day, the CDC released information from the National Youth Risk Behavior Survey showing that while cigarette smoking was at an all-time low for high school students since 1991, 24% of them reported using e-cigarettes during the previous 30 days.
"Current cigarette smoking is at an all-time low, which is great news. However, it's troubling to see that students are engaging in new risk behaviors, such as using e-cigarettes," CDC Director Tom Frieden said. "We must continue to invest in programs that help reduce all forms of tobacco use, including e-cigarettes, among youth."
In July, more proof of rising use among youth: A study published in Pediatrics looked at cigarette use over a 20-year period by Southern California 11th- and 12th-graders and found that e-cigarettes may well be a gateway drug. That's dangerous, said the researchers, because it means e-cigarettes are "recruiting a new group of users who would not likely have initiated combustible tobacco product use in the absence of e-cigarettes, which poses a potential threat to the public health of adolescent populations."
Another study, also published in Pediatrics, showed that teens using these flavored versions were less likely to see tobacco smoking as dangerous and therefore more likely to take up cigarette smoking. Quoting Department of Health and Human Services data, the study also said an estimated 5.6 million youth could die early from cigarette smoking-related illness unless youth smoking rates drop dramatically.
In August, researchers found that vaping for 30 minutes could be just as bad for the human heart as smoking cigarettes. A team from the Hippokration General Hospital in Athens, Greece, at the European Society of Cardiology's annual congress presented findings from a small study in which they monitored the hearts of 24 smokers who smoked both regular cigarettes and e-cigarettes for either five or 30 minutes, with the latter considered the average time someone spends vaping.
Smoking an e-cigarette for 30 minutes was found to affect the stiffness of the heart's main artery, the aorta, to a similar extent as smoking a regular cigarette for five minutes. This added stiffness increases the risk of cardiovascular disease.
Professor Peter Weissberg, medical director at the British Heart Foundation, who was not involved in the research, said the study "shows that electronic cigarettes cannot be assumed to be risk-free. Much more research is needed to establish the safety of long-term use of these devices."
Former smokers who replaced standard cigarettes with e-cigarettes substantially reduced their intake of cancer-causing chemicals, according to a study published in Annals of Internal Medicine in February.
Although it's clear that vaping is not a healthy behavior, many people argue that it is at least better than smoking. Yet scientific evidence of how these two behaviors compare has been sorely lacking.
A long-term study funded by Cancer Research UK compared exposure to nicotine, tobacco-related carcinogens and toxins among five groups of people, including those who smoked only traditional cigarettes; former smokers who became long-term e-cigarette users; and former smokers now using nicotine patches, gums and other products. Participants provided urine and saliva samples. The researchers also analyzed biomarkers for nicotine and cancer-causing ingredients and other toxins.
The UCL researchers in the UK discovered that all the groups had similar levels of nicotine.
However, long-term users of e-cigarettes had lower levels of tobacco-related carcinogens and toxins than traditional cigarette smokers. In fact, when smokers switched completely to e-cigarettes, their intake of cancer-causing chemicals dramatically fell to a level found in people using nicotine replacements, the researchers found.
"It's an impressive study," said Andrea Spatarella, a nurse at the Center for Tobacco Control at Northwell Health in Great Neck, New York, who was not involved in the research.
Still, it has weaknesses, such as too few participants and irregular sample-taking times, she said. When participants drink coffee or even use mouthwash, this can alter a sample. She also noted that the study did not account for the harms of chemicals in e-cigarettes.
Based on her own research, Spatarella said most people who attempt a complete switch fail and ultimately become dual users. "We've had very, very few who were successful in using e-cigarettes as a cessation device."
Data, released in the UK has shown a decline in smoking rates simultaneous with a rise in people taking up vaping, with half of them reporting to switch to e-cigarettes to help them quit. Unlike some countries, such as Finland, the UK has supported the promotion of e-cigarettes as an aid to quitting.
Vaughan Rees, director of the Center for Global Tobacco Control at the Harvard T.H. Chan School of Public Health, believes that e-cigarettes can be a useful tool to help people quit smoking and advocates the UK's stance on harm reduction. But his support ends when flavors are involved, following the gateway argument. "We're seeing a proliferation in flavors, including gummy bear and candy flavors that are intrinsically appealing to children." He believes it's "absolutely crucial" that use of these flavors is not endorsed.
The Food and Drug Administration announced that it will regulate all tobacco products, including e-cigarettes, cigars, hookah tobacco and pipe tobacco, and will prohibit the sale to youths under the age of 18. But the regulations stopped short of regulating flavorings, which some say can help adults who are trying to kick their smoking habit. Critics say that leaves these alluring flavors on the market to entice kids to try e-cigarettes.
In February, researchers from George Washington University and the UCSF Center for Tobacco Control Research and Education found that daily e-cig usage doubled the risk of heart attack. If e-cigarette smokers also continued to smoke regular cigarettes, their risk compounded by a factor of five.
"The finding of increased heart attack risk for e-cigarette use, in addition to the risks of any smoking, is particularly troubling, because most people who use e-cigarettes continue to smoke cigarettes," Glantz, the senior study author, said in a statement. The study analyzed data from the 2014 and 2016 National Health Interview Surveys of nearly 70,000 Americans.
One reason, the researchers said, is that although e-cigs contain lower levels of carcinogens than regular cigarettes, they have high levels of "ultrafine particles and other toxins that have been linked to increased cardiovascular and non-cancer lung disease risks -- which account for more than half of all smoking-caused deaths."
The good news, Glantz said, is that stopping smoking immediately drops the risk for heart attack: "Our study also shows little risk associated with being a former e-cigarette user."
A week later, a study published in Pediatrics found that e-cigarette vapor can contain up to five cancer-causing toxins. Analyzing the saliva and urine of teens 13 to 18 who had smoked e-cigarettes recently, researchers from the University of California found significantly higher levels of benzene, ethylene oxide, acrylonitrile, acrolein and acrylamide in the teens who smoked e-cigs than those who did not; if they also smoked cigarettes, the levels were even higher.
Another study in Pediatrics found that youth who experiment with e-cigarettes were nearly two times more likely to become established smokers of regular tobacco cigarettes.