The research, published as an open-access paper in the journal Heliyon, was carried out by a team at the University of Queensland led by Min-Tz Weng and Kathryn Steadman. It is the first investigation to compare the nicotine metabolite ratio, a standard biomarker of nicotine metabolism, between cigarette smokers and users of nicotine vaping products in an Australian population. The finding aligns with three earlier studies from the United States and Spain, which likewise reported no difference in metabolism speed between the two consumer groups.

The biology behind the measurement hinges on a single liver enzyme. Roughly 70 to 80 percent of the nicotine absorbed from any inhaled product is converted into a compound called cotinine, and the same enzyme, CYP2A6, then transforms cotinine into 3-hydroxycotinine. Because cotinine is only turned into 3-hydroxycotinine through CYP2A6 activity, the ratio of total 3-hydroxycotinine to free cotinine in urine, known as the nicotine metabolite ratio or NMR, provides a reliable window into how quickly a person processes nicotine. A high ratio marks a fast metaboliser; a low ratio marks a slow one.

Decades of research in smokers have shown that this ratio matters clinically. People with higher NMR values tend to smoke more cigarettes, absorb more nicotine, and struggle more when attempting cessation, because their nicotine levels drop faster and trigger stronger cravings. In principle, a simple urine test could help clinicians match would-be quitters to the most effective therapies, with fast metabolisers often faring better with certain forms of nicotine replacement than others. Sex and ethnicity also leave fingerprints on the ratio: women typically metabolise nicotine faster than men, and White and Latino populations faster than Asian and African-American populations, partly reflecting inherited differences in CYP2A6 genes.

What has been missing is data on vapers, and on Australian users generally. Previous comparisons of NMR between smokers and vapers had been limited to a large cohort of primarily White women in the US, a smaller group from the American Indian population, and an adult sample in Barcelona measured through saliva. The only prior Australian measurement came from a methods-validation study of 280 Tasmanian smokers, without any within-cohort comparisons. The Queensland team set out to fill both gaps at once.

The researchers recruited 44 adults in Brisbane who used either conventional cigarettes or nicotine vaping products exclusively, at least daily. Each participant kept a three-day diary recording brands, strengths, flavours and consumption, then collected every drop of urine over a full 24-hour period on the third day. After excluding two vapers whose cotinine levels fell below a biochemical threshold confirming active nicotine use, the final analysis covered 42 people: 22 smokers and 20 vapers. Most were male, aged 18 to 29, and ethnically diverse, including Asian, White, Latino and one Australian Aboriginal participant.

The laboratory work was exacting. Urine samples were diluted, split, and analysed by liquid chromatography with tandem mass spectrometry, a technique sensitive enough to detect metabolites at concentrations below a tenth of a microgram per litre. Half of each sample was treated with an enzyme that strips off glucuronide conjugates, allowing the team to measure total nicotine, cotinine and 3-hydroxycotinine, six compounds in all, summed as total nicotine equivalents. Creatinine measurements normalised the results for differences in hydration. The overall mean NMR of 2.71 sat comfortably within the range of 1.7 to 5.2 reported in earlier populations worldwide.

The headline result was a null finding with real weight: urinary NMR did not differ between smokers and vapers. Metabolism speed, it appears, is a property of the person, not the product. But exposure told a different story. Vapers excreted significantly higher concentrations of cotinine and 3-hydroxycotinine, and consequently higher total nicotine equivalents, whether expressed per milligram of creatinine or per 24-hour urine volume. The authors suggest this reflects the higher nicotine content of vaping liquids and their enhanced palatability, which can encourage more frequent and deeper intake. Consistent with national Australian survey data, the vapers were also significantly younger than the smokers, averaging 26 years against 34.

Within the cohort, the expected demographic patterns emerged. Women averaged an NMR of 3.49 compared with 2.43 in men, a statistically significant difference, and participants of White background averaged 2.99 against 1.94 for those of Asian descent, echoing the known prevalence of reduced-function CYP2A6 variants among Asian populations. Splitting the group at the median ratio of 2.31, the researchers found that faster metabolisers carried higher concentrations of cotinine, 3-hydroxycotinine and total nicotine equivalents than slower ones, exactly as predicted by the wider literature. Intriguingly, the single Australian Aboriginal participant, a woman using cigarettes, posted one of the highest ratios recorded, at 5.25, a hint of variation in a population for which no NMR data previously existed.

The authors are candid about the study’s limits. Forty-two participants is a small sample, and the sex and ethnicity subgroup analyses are exploratory. Factors known to shift the ratio, such as menthol ingredients, CYP2A6-altering medications, pregnancy and alcohol, were not assessed, and the unsupervised at-home urine collections mean the 24-hour totals deserve cautious interpretation. Still, the message for the fast-growing population of vapers is clear: their bodies handle nicotine no differently than smokers’ bodies do, even as modern devices deliver a heavier dose. If the nicotine metabolite ratio proves useful for tailoring cessation therapy, that guidance should apply equally to anyone trying to give up vaping.

Subject of Research: Nicotine metabolism rate measured by urinary nicotine metabolite ratio in cigarette smokers versus nicotine vaping product users

Article Title: Exploring nicotine metabolism among people who smoke and vape

Article References: Weng, M.-T., Zheng, Q., Deng, Y., Shrestha, S., Fan, W., Thai, P. K., Gartner, C. E., & Steadman, K. J. (2026). Exploring nicotine metabolism among people who smoke and vape. Heliyon, 12(15), Article e45549. https://doi.org/10.1016/j.heliyon.2026.e45549

Image Credits: AI Generated

DOI: 10.1016/j.heliyon.2026.e45549

Keywords: nicotine metabolism, CYP2A6, nicotine metabolite ratio, cotinine, 3-hydroxycotinine, vaping, cigarette smoking, smoking cessation, LC-MS/MS, urine biomarkers, Australia, nicotine exposure