Where we stand now: E-cigarettes

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— A growing number of studies illustrate the dangers of e-cigarette use by adolescents, claiming they can serve as a gateway for future tobacco use by our nation’s youth.

The latest research on the subject, published in Pediatrics, says e-cigarette use by teens during 2014 was on the rise, mostly fueled by kid-pleasing fruit and candy flavors such as “candy crush, gummy bear and bubble gum”. The study showed the 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.

The Food and Drug Administration recently 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.

The FDA recently cracked down on e-cigarette retailers, sending warning letters to 55 marketers who were continuing to sell e-cigarettes, hookah tobacco and other tobacco products to minors.

E-cigarettes 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 — and some studies have shown that it helps smokers quit. In fact, many e-cigarette users don’t call themselves smokers, preferring to use the term “vapers” instead.

Despite research showing a danger to adolescents, there remains a controversy over long term impact of e-cigarettes and how they should be regulated. Are they really an effective way to quit smoking? Does “vaping” introduce health issues all its own, unrelated to tobacco? 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:

2003 headline: Invention of e-cigarettes

Three pack-a-day smoker Hon Lik, a 52-year-old Beijing pharmacist, creates the first successful electronic cigarette after his father, another heavy smoker, dies of lung cancer. By 2007, e-cigarettes are marketed in Europe and the United States by the manufacturer Ruyan as a way to safely stop smoking tobacco.

Hon is 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.

2008 headline: WHO slams e-cigarette marketing

In September 2008, the World Health Organization announces 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 declares the product to be 100 to 1,000 times less dangerous than smoking tobacco, adding that when using their device, nicotine is “apparently not absorbed from the lung, but from the upper airways.”

2010 headline: The battle heats up

In May 2009, the Food and Drug Administration releases the results (PDF) of a test of two U.S. e-cig brands, NJOY and Smoking Everywhere, that finds “very low” amounts of nicotine in cartridges labeled as nicotine-free. Then in July, an FDA news release discourages 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, non-toxic 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 restrict the sale of e-cigs on their websites.

2011 headline: Interest in vaping for smoking cessation is high

Science begins to ramp up studies on the topic. Several studies find interest in e-cigarettes is high among the American public: Google searches for e-cigs are higher in the U.S. than any other nation.

A questionnaire of 3,500 e-cigarette users finds that most vape because they think it is less toxic and cheaper than tobacco, and will help them quit or cut down on tobacco smoking. Most ex-smokers (79%) in the study are afraid they will relapse if they stop using e-cigarettes. The study doesn’t examine the safety of the product.

Another, much smaller email study of 216 e-cigarette users finds that 31% were tobacco free at six months, while 66% were able to cut back on the number of conventional cigarettes they smoked. A still smaller study of 40 smokers also finds that adding e-cigarettes helped smokers reduce the number of traditional cigarettes they smoked each day.

2012 headline: E-cigarette use doubles in adolescents

The Centers for Disease Control announces that e-cigarette use among U.S. middle and high school students doubles 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 test 16 e-cigarettes with an automatic smoking machine and find wide variations in nicotine levels per puff, ranging from 0.5 to 15.4 mg. In contrast, the typical level from a tobacco puff ranges only from 1.54 to 2.60. The wide variation between e-cigarette brands leads researchers to question how well they can function as a nicotine replacement device.

2013 headline: Do e-cigs really help smokers quit?

Several 2013 publications show minimal evidence that e-cigarettes help smokers quit. A cross-sectional study of 1,836 tobacco smokers finds a significant association with e-cig use and “unsuccessful quitter” status but none with ‘quitter” status.

Another study of callers to state tobacco quitlines finds e-cigarette users significantly less likely to be tobacco-free seven months after they first try vaping compared with participants who never try e-cigarettes.

A New Zealand Health Research Council study of 657 smokers finds e-cigarettes modestly effective in helping smokers quit. Interestingly enough, it didn’t seem to matter whether they contained nicotine or not. But the results were similar to already FDA approved nicotine patches.

Some researchers worry 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 say in their essay “The Emergence of E-Cigarettes: A Triumph of Wishful Thinking over Science.”

2014 headline: Poison center calls skyrocket

The Centers for Disease Control releases 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 finds e-cigarette use to be strongly associated with current and heavy traditional cigarette smoking. Data from the CDC find that the use of e-cigarettes among U.S. high school students grew from 4.5% in 2013 to 13% in 2014. In that same time 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 finds the e-cig version a clear winner with users, providing more satisfaction and a better image.

In regard to safety, a study finds that e-cigarettes do contain tobacco-specific nitrosamines and heavy metals like cadmium, nickel and lead, but the levels are 9 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 aren’t convinced. “Although these data suggest that e-cigarettes may be a safer alternative to conventional cigarettes,” say reviewers Bradley Drummond and Donna Upson, “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.”

2015 headline: Vaping could be dangerous, but perhaps a quitting aid

A New England Journal of Medicine study sets 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 restates ongoing concerns about propylene glycol, or PG, and the various food flavorings that are part of e-juice. While considered safe to eat in food in small quantities, researchers say PGs have not been studied when “inhaled deeply and repeatedly.”

Another study looks 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 finds diacetyl at higher than laboratory normal levels in 39 of the tested flavors. Researchers call for “urgent action” to evaluate the “potentially widespread exposure.”

In September, new research from the prestigious medical journal BMJ finds that teens who use e-cigarettes are 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 towards cell death.

However, a 2015 report by Public Health England (PDF) encourages 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, finds that e-cigs “could have helped several hundreds of thousands” quit smoking, at least temporarily.

2016 headline: Vaping a gateway to tobacco use … and no better for your heart

In late January, BMJ published a study (PDF) 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 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.

While the study showed 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 currently 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 past 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.”

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.”

2017 headline: E-cigarettes are safer than conventional cigarettes

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 University College London researchers 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 North Shore-LIJ Health System 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.

“This study was focused on cancer as this is the major disease caused by smoking cigarettes,” wrote Lion Shahab, lead researcher of the study and a senior lecturer at University College London, in an email. “Our findings should provide some reassurance to cigarette smokers who want to reduce their risk of smoking-related disease that switching over to e-cigarettes completely is likely to carry substantial health benefits long-term.”

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.”

CNN’s Meera Senthilingam contributed to this report.