Biomarkers Don't Lie: Teen Vapers Get As Much Nicotine As Smokers

A population-based biomarker study published in JAMA Network Open found that among 16- to 19-year-olds, exclusive vaping behavior produced similar levels of nicotine in the body as cigarette smoking. And among “vapers only,” use of nicotine salt e-liquids was associated with even higher levels of nicotine exposure.

Background

In recent years, teen use of e-cigarettes has increased. New formulas and devices (especially those with nicotine salts) make the vapor softer, allowing for higher doses of nicotine to be inhaled without throat irritation. With uneven regulations in different countries and a rapidly changing market, a basic question arises: what is the real “nicotine load” of teen vapers compared to smokers?

Why biomarkers are better than surveys
Teenagers' self-reports of the "number of puffs" and "strength" of liquids are inaccurate: cartridges, puff speed, and device power change. Therefore, objective biomarkers of nicotine in urine are used:

• Cotinine and trans-3'-hydroxycotinine are stable metabolites of nicotine, reflecting exposure over the past 1-3 days.
• TNE-2 (sum of two metabolites, usually adjusted for creatinine) is an integrated assessment of total nicotine exposure.

These indicators allow us to compare groups (vaping only, cigarettes only, dual use, no use) without relying on respondents' memory.

Why the emphasis on "nicotine salt"
Free nicotine ("free-base") at high concentrations gives a "burning" vapor; salt forms (nicotine salt) "buffer" the vapor, reduce irritation and increase the transfer of nicotine in the same puff. In a teenage audience, this can accelerate the formation of addiction despite the apparent "softness" of the product.

Design that closes the gaps
Comparing teens from multiple countries (Canada, England, USA) and dividing them into pure behavioral groups (“vape only,” “cigarette only,” “dual users,” “non-users”) provides a rare opportunity to:

• to assess the real, biochemically confirmed nicotine load in everyday life;
• understand the contribution of product type (salt vs. unsalted) and not just the nominal "strength" of the liquid;

• Compare results against the background of differences in policy and product range.

What was already known before

• Adult vapers often have nicotine levels comparable to smokers, but adolescent data have been limited and fragmented.
• Saline liquids were hypothesized to increase nicotine uptake and risk of addiction in young people, but population biomarkers rather than laboratory models were needed.

Why do practitioners need such results?

• It is important for pediatricians, schools, and families to talk to teens not just about “taste” and “pretty devices,” but about the actual nicotine load, which can be as much as cigarettes.
• It is useful for regulators and prevention programs to focus on nicotine form (salt/non-salt) and objective markers of exposure - this is more accurate than counting "puffs".

Key methodological caveat:
Biomarker studies in adolescents are typically cross-sectional: they are good at showing the level of exposure in the here and now, but do not answer questions of causality and long-term clinical outcomes. For this, longitudinal cohorts and expanded marker panels are needed.

What was studied and how

• Who: 364 teenagers aged 16-19 from Canada, England and the USA.
• When: collection from September 2019 to January 2022.
• Design: Cross-sectional (observational) study; participants completed a questionnaire and self-collected morning urine.
• Groups: in the last week - none (neither vape nor tobacco), only vape, only smoke, dual use.
• What was measured: urine nicotine markers - cotinine, trans-3'-hydroxycotinine and their sum (TNE-2), all adjusted for creatinine (to account for dilution).
• An important detail for vapers: they were asked whether the last device contained nicotine in the form of salts and what concentration of nicotine was indicated (≤20 mg/ml, >20 mg/ml).

Why TNE-2? It is a more "complete" assessment of the accumulated nicotine intake than cotinine alone: you add up the two main metabolites - you get a more reliable result.

Main results

1) Vaping ≈ smoking by nicotine load

• TNE-2 (geom. mean)
  - vaping only: 3.10 nmol/mg creatinine
  - smoking only: 3.78
  - dual use: 6.07
  - non-user: 0.19
• No statistically significant differences were found between "vaping only" and "smoking only" (as well as "double"); all three "nicotine" groups were significantly higher than "not used".

Conclusion: for teenagers of the current generation of devices, vaping ≠ "low nicotine". According to biomarkers, this is a level comparable to cigarettes.

2) Nicotine salts - a dose "accelerator"

Among those who only vaped:

• With salt nicotine, TNE-2 was several times higher: 10.78 nmol/mg versus 2.72 with non-salt liquids and 1.55 if the teenager did not know the type. The relationship remained after adjustments.
• However, simply dividing by concentration (>20 mg/ml vs ≤20 mg/ml) did not yield a clear difference in TNE-2. In other words, the form (salt vs “free” nicotine) is more important than just the number on the label.

3) Countries

Levels were broadly similar between Canada, England and the US; small differences among smokers (lower in Canada than in England) did not make a difference.

Why is this important?

• Addiction: Since nicotine exposure in adolescent vapers is comparable to that of smokers, the risk of developing addiction and long-term trajectories of use is high.
• Role of salts: Salt formulas are gentler on the palate/throat and facilitate deep draws - ultimately delivering more nicotine. This supports laboratory and population data on the greater "stickiness" of salt devices.
• Regulatory: mg/ml limits alone are not enough. It makes sense to differentiate:
  1. form of nicotine (salt vs freebase),
  2. clear markings on the device,
  3. restricting the sale of high dose/salt devices to adolescents.

What this does not prove

• The study is cross-sectional: we see a cross-section, but cannot establish causality.
• Self-reports: nicotine type/concentration - self-reported; packaging and market labelling often confusing.
• The size of the subgroups (e.g. pure salt vapers) is not huge; biomarkers are from one morning portion.

However, the picture is consistent with what we know about salt liquids and their ability to deliver nicotine at cigarette levels.

Practical conclusions

For parents and schools

• “These aren’t cigarettes” is a weak argument: the nicotine levels are comparable.
• Keep track not only of “how many minutes you vape,” but also what exactly: pod devices with salts are a special risk zone.
• Conversations ≠ prohibitions: work with motivation, stress alternatives and companies where it’s “okay not to fuck around.”

For doctors

• Add a couple of questions about device type and liquid (salt/non-salt) to teen screening.
• Signs of addiction (morning "first puffs", difficulties in quitting) are not uncommon among vapers and require the same seriousness as among smokers.

For regulators

• Consider mandatory large markings on the device/cartridge itself with the form and concentration of nicotine.
• Discuss limits for salt forms and control of sales channels (including third parties, marketplaces, social networks).

Summary

Teen vaping in the 2020s is no longer a “light version” of nicotine. In terms of biomarkers, the nicotine load is comparable to cigarettes, and salt liquids significantly increase it even more. If the goal is to really reduce the risks for teenagers, fighting milligrams per milliliter alone will not do: transparent labeling, taking into account the form of nicotine, and working with availability are needed.

Source: Hammond D. et al. JAMA Network Open (2025 Mar 3; 8(3):e2462544); PubMed/PMC; JAMA Network Open March issue page. doi:10.1001/jamanetworkopen.2024.62544