Mango. Crème brûlée. Cucumber. Mint. No, these aren’t just ice cream flavors. They are some of the flavors enticing kids and adults to vape.

Even as rates of smoking combustible tobacco cigarettes continue to decline, millions of Americans are now using electronic cigarettes (more commonly known as e-cigs, vapes, personal vaporizers, e-hookahs, mods, vape pens and — more recently — pod-based products such as “Juul”). Many people believe that e-cigarettes represent a “safe” alternative to smoking tobacco cigarettes. But what are the facts, and what do we still not know for sure?

To find answers, HealthySteps to Wellness analyzed the clinical data and spoke with Bonnie Halpern-Felsher, PhD, Professor of Pediatrics in the Division of Adolescent Medicine at Stanford Medicine and the founder and executive director of the Stanford Medicine Tobacco Prevention Toolkit, an online curricular aimed at reducing and preventing youth tobacco use; and Anna Lembke, MD, Assistant Professor and Chief of Addiction Medicine at the Stanford University School of Medicine. We also examined the work of Robert Jackler, MD, the Sewall Professor of Otorhinolaryngology and Professor, by courtesy, of Neurosurgery and of Surgery at the Stanford University School of Medicine. Dr. Jackler and his wife Laurie founded the interdisciplinary research group SRITA (Stanford Research Into The Impact of Tobacco Advertising).

Highlights

• Even though they were not marketed broadly until 2007, e-cigarettes are now smoked by millions of Americans, and use by adolescents and young adults has and is continuing to surge.
• Because e-cigarettes do not contain tar, many people consider them safer than combustible cigarettes. (Manufacturers/marketers hope and claim that their e-cigarette products might represent a way for some current tobacco smokers to wean themselves off of tar-filled combustible cigarettes; however, at present there is no strong clinical evidence of this benefit.)
• However, “safer does not mean safe.” E-cigarettes contain large quantities of nicotine, a highly addictive substance that has health implications for us all. Nicotine addiction is known to have an especially adverse impact upon the developing brains of individuals under the age of 25. (We detail this and other adverse effects of nicotine in the heart of this report and in our Addendum.)
• Because the nicotine level in e-cigarettes is so significant, addiction can occur quickly, and there is evidence that this addiction increases the likelihood that a user will ultimately become a smoker of combustible cigarettes, known to cause cancer and many other negative health outcomes.
• E-cigarettes also contain other chemicals, most notably flavorants, that scientists increasingly fear may put users at risk for adverse health effects.
• Large and carefully controlled long-term research studies on the health impact of e-cigarettes may be years away from completion, and the variety of different e-cig products makes such research difficult at best. Meanwhile, the Food & Drug Administration (FDA), even though it has raised significant concerns about the safety of e-cigarettes, has not imposed regulations governing the making nor marketing of e-cigarettes, except to say it intends to “crack down” on retail outlets “caught” selling them to those who are under-age.
• Therefore, all users of e-cigarettes should be aware that they are “vaping at their own risk.”

What are e-cigarettes?

Electronic cigarettes (also known as vapes, vaporizers, or vape pens and — more recently — pod-based products such as “Juul”) are generally battery-powered products that heat liquid into an aerosol that is inhaled by the user. These devices are designed to deliver (1) nicotine, (2) flavors, and (3) they also contain chemicals such as propylene glycol, glycerin, and many other constituents — depending on the brand and type of device.

E-cigarettes come in all shapes and sizes, some looking very similar to regular cigarettes. Right now, 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 and other chemicals. However, in the last few years, the look and feel of vaping devices has changed dramatically. Juul Labs, a San Francisco based company with the leading market share among e-cigarette products, has designed arguably the sleekest, most attractive, and to kids the “coolest” vaping pen on the market — it is a mere 4 inches in length and is flat, rectangular and resembles a USB stick. The Juul, which hit the market in 2015, comes with pre-filled containers of nicotine liquid, known as pods. Young people appear to be especially drawn to the device, which is discrete enough to hide. In this video, How e-cigarettes like the Juul are coopting the language of wellness, Stanford professor Robert Jackler, MD, describes the marketing allure of these newer e-cigarette devices.

Surging popularity of newer e-cigarette vaping sticks and pods

Even as rates of smoking combustible tobacco cigarettes continue to decline among youth and adults, e-cigarette use has surged. In a 2015 report, the California Department of Public Health stated that e-cigarette use among young adults (ages 18 to 29) tripled in just one year from 2.3 percent to 7.6 percent in 2014, and a whopping 17% of 12-graders in that year reported being users. And this is 2014 data.

The Centers for Disease Control (CDC) estimated that in 2016, the most recent year of available CDC data, 3.2% of U.S. adults were current e-cigarette users. Alarmingly, high school use was 11.3% in 2016; and 4.3% of middle schoolers used e-cigarettes — even though the minimum legal age “required” to purchase e-cigarettes is 18 in most states (and 21 in California, Oregon and Hawaii).

While 2017 CDC data are not yet available, most market observers predict that high school and middle school use rose significantly this past year, once again. Clearly, the new generation of e-cigarette devices, like the Juul, is fueling the frenzy. As described in a recent The San Francisco Chronicle  article, “Juuls appear to have ushered in a cultural phenomenon among teens, a trend fueled by the addictive power of nicotine, the ease of acquisition and the pull of peer pressure.” ¹

What exactly is in an e-cigarette, and what are the health concerns?

1. Nicotine: The heart of an e-cigarette

(See also our  Addendum, at the end of this article, for a more detailed summary of nicotine: what it is, how it works in the body and brain, health risks and what it means to be addicted.)

As Bonnie Halpern-Felsher, PhD, explains, “The amount of nicotine in typical e-cigarettes varies significantly, from 0 to about 12 mg of nicotine (and as high as around 36 mg). Juul, a pod-based product, contains 59 mg of nicotine per pod — the amount of nicotine that is in a pack of cigarettes.” On its website, Juul Labs actually touts the fact that its pod contains an equivalent amount of nicotine to combustible cigarettes:

“JUUL Labs was founded with the goal of improving the lives of the world’s one billion adult smokers by providing them with an easy to use vapor alternative to combustible cigarettes, containing a similar level of nicotine to make switching as easy as possible.”

Halpern-Felsher cautions that “the actual amount of nicotine one ingests and is affected by depends largely on the type of e-cigarette device. There are numerous types of devices, varying by voltage, size, ability to alter, and so on.” The newer devices, such as the Juul, contain salt-based nicotine that makes it easier to inhale. However, Halpern-Felsher insists that “that doesn’t make it safer than other e-cigarette/vaping devices or cigarettes. There is still a tremendous amount of nicotine in these devices, and nicotine can definitely negatively impact the brain and is the component in these products that make one addictive.”

The greatest dangers of nicotine

When we asked Halpern-Felsher to sum up what makes nicotine so dangerous, she cited the following:

• Nicotine interferes with the healthy development of the adolescent and young adult brain
• Nicotine can hijack the reward pathway in the brain
• Nicotine causes addiction

Clearly, children and young adults are at the most risk from inhaling nicotine: “The parts of the brain most responsible for cognitive and psychosocial maturity continue to develop and change through young adulthood, and adolescent brains are uniquely vulnerable to the effects of nicotine.” ²

While most states have passed laws forbidding retail outlets from selling e-cigarettes to those under 18 (and, in California and a few other states, you must be 21), there’s no guarantee that a brain will have stopped developing at these ages. In fact, most top scientists, including Halpern-Felsher and Lembke, believe there is ample evidence indicating that brains are still developing up to age 25.

As Halpern-Felsher explains, “since the brain continues to develop until about age 25, one is most at risk of becoming addicted during this time. During this time of brain development, the brain actually changes when exposed to nicotine. Nicotine receptors are more likely to be stimulated and addiction is much more likely to occur.”

When we analyzed the medical literature on brain changes from nicotine, we found that the majority of scientists deem such brain changes as permanent in nature, a view corroborated by Halpern-Felsher. What are some of the symptoms of these permanent changes? Lembke observes that nicotine addiction can result in insomnia, irritability, and can create barriers around studying and learning. Similarly, Nicholas Chadi, a clinical pediatrics fellow at Boston Children’s Hospital (who spoke about Juul at the American Society of Addiction Medicine’s annual conference in January 2018), stated that the brain changes resulting from nicotine addiction are also linked with increased sensitivity to other drugs, as well as greater impulsivity ³.

Nicotine as an addiction gateway

Of great clinical concern is that nicotine addiction could drive an e-cigarette user to pick up combustible cigarettes. What if you’re at a party and your Juul pod is empty, and someone nearby offers you a combustible cigarette just when you are feeling the effects of a nicotine craving or the compulsive tendencies that occur when you are in nicotine withdrawal? Are you going to refuse the cigarette? This quote from a recent analysis says it all:

“Nicotine addiction is the proximate cause of disease and death from cigarette smoking.” ⁴

Researchers at the University of Southern California’s School of Medicine found that “e-cigarette use in never-smoking youth may increase risk of subsequent initiation of cigarettes and other combustible products during the transition to adulthood when the purchase of tobacco products becomes legal.” ⁵ In fact they found that teens who do vape are six times more likely as those who have never vaped to later begin smoking.

Many vapers, posting on social media, state insistently that some scientists are being “melodramatic” in “jumping to the conclusion” that nicotine addiction from e-cigs becomes “a gateway” to use of other drugs, or to use of combustible cigarettes.  Halpern-Felsher’s view: “There are many  studies showing that adolescents who begin using tobacco with e-cigarettes/vapes are more likely to later use cigarettes than non-vape users… in fact, there is ample evidence from longitudinal studies that this is happening.” Her view is corroborated by the NAP report, a major retrospective of 5,000 clinical research studies done on e-cigarettes:

“There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults. . . . Taken together the evidence suggests that while e-cigarettes might cause youth who use them to transition to use of combustible tobacco products, they might increase adult cessation of combustible tobacco cigarettes.” ⁶

While the data are preliminary, Lembke and Halpern-Felsher both fear that nicotine addiction also could make individuals more vulnerable to other addictions.

Even though it is theoretically possible, maybe even logical to assume, that e-cigs could help current tobacco smokers wean themselves off combustible, tar-filled cigarettes — the stated mission of market-leader Juul Labs — the clinical evidence of this “benefit” is scant. The CDC states it this way:

“E-cigarettes are not currently approved by the FDA as a quit smoking aid. The U.S. Preventive Services Task Force, a group of health experts that makes recommendations about preventive health care, has concluded that evidence is insufficient to recommend e-cigarettes for smoking cessation in adults, including pregnant women….To date, the few studies on the issue are mixed. A Cochrane Review found evidence from two randomized controlled trials that e-cigarettes with nicotine can help smokers stop smoking in the long term compared with placebo (non-nicotine) e-cigarettes. However, there are some limitations to the existing research, including the small number of trials, small sample sizes, and wide margins of error around the estimates. A recent CDC study [PDF–197 KB] found that many adults are using e-cigarettes in an attempt to quit smoking. However, most adult e-cigarette users do not stop smoking cigarettes and are instead continuing to use both products (known as ‘dual use’). Dual use is not an effective way to safeguard your health.”

Halpern-Felsher sums it up this way: “There is no evidence that Juuls help people quit smoking. Even if they did, to me, the concerns of youth initiating tobacco through Juuls outweighs any potential adult benefit.”

2. The flavorants

Beyond the major concern of nicotine in e-cigarettes, Halpern-Felsher and others are “very worried about the flavorants in e-cigarettes. There is a great deal of evidence showing that the flavorants (e.g., buttery flavors, cinnamdaldehyde) alone are harmful.” So concerned were Halpern-Felsher and a consortium of other scientists and doctors that, earlier this year, they wrote the FDA and pleaded for regulation of e-cigarettes specifically because of the harms associated with the flavors:

“…. [There are] numerous cross-sectional and longitudinal studies focusing on combustible cigarettes, smokeless tobacco, cigars, and e-cigarettes showing that youth are attracted to flavored tobacco products, more susceptible to initiating and using tobacco, and more likely to actually use tobacco with flavors. Conversely, youth are significantly less likely to use tobacco if unflavored. Further, there is clear evidence from human and animal studies that the flavorants used in tobacco is responsible for health consequences, including health effects observed in and outside of the respiratory system. In contrast, there is very little and inconsistent evidence that flavored tobacco helps adults quit combustible cigarettes. The published data generally show that adults are not attracted to flavors, and that those who attempt to quit cigarette use via e-cigarettes or other flavored products are less likely to quit.” ⁷

3. Metals and other ingredients

While ingredients in e-cigarettes do vary greatly by brand, the NAP report states that “There is conclusive evidence that in addition to nicotine, most e-cigarette products contain and emit numerous potentially toxic substances.” ⁶

NAP does state that early data “suggests that e-cigarette aerosol contains fewer numbers and lower levels of toxicants than smoke from combustible tobacco cigarettes.” However, once again, less toxic does not mean no toxicity. As one recent study states, “Only a few studies have addressed exposure to metals through e-cigarette aerosol.” This study was relatively small and looked only at certain types of devices, but found that “e-cigarettes are a potential source of exposure to toxic metals (Cr, Ni, and Pb), and to metals that are toxic when inhaled (Mn and Zn). Markedly higher concentrations in the aerosol and tank samples versus the dispenser demonstrate that coil contact induced e-liquid contamination.” ⁸

Once again, more research needs to be done here, so users must accept the fact that they are vaping at their own risk.

4. Cardiovascular and other system effects

The NAP report concludes that there is “insufficient evidence” to suggest cardiovascular harm from e-cigarettes.^6.However, well-controlled and larger, longitudinal studies have yet to be done. Halpern-Felsher notes that already “there is some evidence showing that e-cigs are related to cardiovascular and respiratory risk and damage… and there are some published articles showing this effect. We simply do not have more definitive data largely because e-cigs haven’t been around long enough.”

Similarly, the long-term consequences of e-cigarette smoking on pulmonary/respiratory function and health, and the risks of cancer and adverse reproductive outcomes, “remain to be determined,” says the NAP report ⁶.

Final thoughts

This report is not aimed at providing a comprehensive analysis of every clinical research study of e-cigarettes. However, users should be aware of what is known and the vast uncertainty regarding what is yet to be known. We do already know of several very clear health risks you take when you vape. Unfortunately, a significant percentage of our population is unaware of or does not accept these known hazards and risks. Of great concern, an important study published about adolescents’ attitudes toward e-cigarettes showed “increased acceptability and positive attitudes towards e-cigarettes”; the study also provided evidence that adolescents harbor many misperceptions — including that e-cigarettes do not contain any or just limited amounts of nicotine.⁹

While we are not convinced that additional regulations and prohibitions will be the  answer to health concerns regarding e-cigarettes, we do believe that education and information are the best ways to (a) distinguish the facts from the fictions and (b) to positively influence behaviors.

By Lane McKenna
September 2018

Footnotes

¹ Tucker J. Teen vaping surges with flavorful Juuls. The San Francisco Chronicle. May 2018.
² Bonnie RJ, Stratton K, and Kwan LY. “Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products” Washington (DC): National Academies Press (US); 2015 Jul 23.
³ Brodwin E. An e-cigarette with twice the nicotine of comparable devices is taking over high schools — and scientists are sounding the alarm. Business Insider. April 2018.
⁴ Benowitz NL, Henningfield JE. Nicotine Reduction Strategy: State of the science and challenges to tobacco control policy and FDA tobacco product regulation. Preventive Medicine. July 2018.
⁵ Barrington-Trimis JL, Urman R, Berhane K, Unger JB, Cruz TB, Pentz MA, Samet JM, Lenventhal AM, McConnel R. E-Cigarettes and Future Cigarette Use. Amer. Academy of Pediatrics: News & Journals Gateway. April 2016.
⁶ National Academies of Sciences, Engineering, and Medicine. 2018. Public Health Consequences of E-Cigarettes. Washington, DC: The National Academies Press. https://doi.org/10.17226/24952.
⁷ Halpern-Felsher B, Lempert LK, Watkins S, Chaffee B, Gotts J, Jacob P, Popova L, Glantz, SA. FDA should implement its proposed rule that manufacturers must present scientific evidence demonstrating that any flavored tobacco product is appropriate for the protection of the public health before receiving marketing authorization to use that flavor. Docket No: FDA-2017-N-6565. May 2018.
⁸ Olmedo P, Goessler W, Tanda S, Grau-Perez M, Jarmul S, Aherrera A, Chen R, Hilpert M, Cohen JE, Navas-Acien A, Rule AM. Metal Concentrations in e-Cigarette Liquid and Aerosol Samples: The Contribution of Metallic Coils. Environmental Health Perspectives. February 2018.
⁹ Gorukanti A, Delucchi K, Ling P, Fisher-Travis R, Halpern-Felsher B. Adolescents’ attitudes towards e-cigarette ingredients, safety, addictive properties, social norms, and regulation. Preventive Medicine 94 (2017) 65–71.

Addendum

A. What is in e-cigarette aerosol?
(source: CDC)

The e-cigarette aerosol that users breathe from the device and exhale can contain harmful and potentially harmful substances, including:

• Nicotine
• Ultrafine particles that can be inhaled deep into the lungs
• Flavoring such as diacetyl, a chemical linked to a serious lung disease
• Volatile organic compounds
• Cancer-causing chemicals
• Heavy metals such as nickel, tin, and lead¹

It is difficult for consumers to know what e-cigarette products contain. For example, some e-cigarettes marketed as containing zero percent nicotine have been found to contain nicotine.

B. What is nicotine, how does it work, and what are the health concerns?
(source: Stanford Tobacco Prevention Toolkit)

• Nicotine is a drug that is a stimulant, meaning it raises levels of physical or psychological activity in the body, and it is toxic at high doses.
• Nicotine is highly addictive since it causes changes in brain chemistry quickly and leaves the brain craving more.
• Nicotine is found in tobacco products and nicotine exposure during fetal development has lasting adverse consequences for brain development as it can affect maternal and fetal health during pregnancy.
• Data from studies of mice suggest that nicotine exposure during adolescence may have lasting adverse effects on brain development.

Nicotine’s affect upon the brain

• When inhaled, nicotine passes through the lungs and then enters into the brain, where it binds to pleasure receptors, causing a release of pleasure chemicals (such as dopamine) that provide the user with a temporary feeling of pleasure. (This might not sound dangerous, but in reality, the nicotine interferes with the body’s natural ability to experience/communicate pleasure.)
• Nicotine use creates floods of dopamine and intense feelings. The pleasure centers in the brain adapt to the drug use by sensing the extra dopamine, and then the brain begins to produce less of it. This means that the user has a hard time creating natural feelings of pleasure without nicotine, and the user needs the nicotine just to feel normal.
• Additionally, the pleasure centers in the brain creates a memory of nicotine and an appetite for it. That appetite for nicotine, even despite its harmful consequences, is what we refer to as nicotine addiction.

Nicotine and the cycle of addiction

• Nicotine is highly addictive. What that means is, the human brain can develop such a strong dependence on the drug that the nicotine user can no longer control their desire or smoking behaviors.
• The cycle of nicotine addiction starts with bringing nicotine into the body. In this case it comes inhalation of cigarettes, hookah, and or e-cigs/vapes.
• Nicotine enters the brain and activates the pleasure centers of the brain.
• After, the level of nicotine in the body drops quickly.
• This drop in nicotine levels causes the body to have a strong craving for nicotine that is satisfied by bringing more nicotine into the body.
• This cycle is powered by the body’s biological reaction to nicotine and isn’t controlled by the person vaping.

Nicotine’s affect upon the body

• Nicotine can make your heart beat faster, because it can activate your “fight or flight response.”
• Nicotine can independently cause trouble breathing and damage to your lungs, outside of all the chemicals and toxins in cigarettes.
• Nicotine can cause you to have increased acid reflux.
• Nicotine can cause insulin resistance, making it potentially more dangerous for those with diabetes.
• Nicotine can even negatively impact your reproductive organs.

C. What is addiction (generally speaking), and why is it a health concern?

Much is misunderstood about addiction, even generally. We think it’s worth defining, and here are two good ones:

“Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because drugs change the brain—they change its structure and how it works. These brain changes can be long-lasting, and can lead to the harmful behaviors seen in people who abuse drugs.” – National Institute on Drug Abuse

“Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because drugs change the brain—they change its structure and how it works. These brain changes can be long-lasting, and can lead to the harmful behaviors seen in people who abuse drugs.” – Stanford Medicine Tobacco Prevention Toolkit

D. Aside from nicotine, what else in e-cigarettes could impact health?
(Source: Stanford Tobacco Prevention Toolkit)

• One of the major appeals of e-cigs/vapes is the over 7,000 flavors of e-liquid available.
• The various trendy flavors have been a very successful marketing strategy that allows e-cig/vape users to consume nicotine without the harsh taste of cigarettes.
• The flavors themselves pose a risk to the e-cig/vape user. Some flavors have been shown to be toxic due to the chemicals they contain.
• The aerosols produced by the chemicals in e-juice, enter into the user’s lungs and leave chemical residue behind.
• Ear, eye and throat irritation is common among e-cig/vape users.