Nicotine Exposure in the U.S. Population: Total Urinary Nicotine Biomarkers in NHANES 2015-2016

Abstract

We characterize nicotine exposure in the U.S. population by measuring urinary nicotine and its major (cotinine, trans-3′-hydroxycotinine) and minor (nicotine 1′-oxide, cotinine N-oxide, and 1-(3-pyridyl)-1-butanol-4-carboxylic acid, nornicotine) metabolites in participants from the 2015−2016 National Health and Nutrition Examination Survey. This is one of the first U.S. population-based urinary nicotine biomarker reports using the derived total nicotine equivalents (i.e., TNEs) to characterize exposure. Serum cotinine data is used to stratify tobacco non-users with no detectable serum cotinine (−sCOT), non-users with detectable serum cotinine (+sCOT), and individuals who use tobacco (users). The molar concentration sum of cotinine and trans-3′-hydroxycotinine was calculated to derive the TNE2 for non-users. Additionally, for users, the molar concentration sum of nicotine and TNE2 was calculated to derive the TNE3, and the molar concentration sum of the minor metabolites and TNE3 was calculated to derive the TNE7. Sample-weighted summary statistics are reported. We also generated multiple linear regression models to analyze the association between biomarker concentrations and tobacco use status, after adjusting for select demographic factors. We found TNE7 is positively correlated with TNE3 and TNE2 (r = 0.99 and 0.98, respectively), and TNE3 is positively correlated with TNE2 (r = 0.98). The mean TNE2 concentration was elevated for the +sCOT compared with the −sCOT group (0.0143 [0.0120, 0.0172] µmol/g creatinine and 0.00188 [0.00172, 0.00205] µmol/g creatinine, respectively), and highest among users (33.5 [29.6, 37.9] µmol/g creatinine). Non-daily tobacco use was associated with 50% lower TNE7 concentrations (p < 0.0001) compared with daily use. In this report, we show tobacco use frequency and passive exposure to nicotine are important sources of nicotine exposure. Furthermore, this report provides more information on non-users than a serum biomarker report, which underscores the value of urinary nicotine biomarkers in extending the range of trace-level exposures that can be characterized.

Keywords: NHANES; exposure; nicotine biomarkers; nicotine metabolites; non-user; tobacco user; total nicotine equivalents (TNE); urine.

Scheme 1

Data attrition and general description of non-user and user populations, in NHANES 2015–2016 (n = 2281). COT = cotinine; HCT = trans-3′-hydroxycotinine; NRT = nicotine replacement therapy; −sCOT = non-users with undetectable serum COT; +sCOT = non-users with detectable serum COT. ^a: Samples with urinary creatinine concentrations outside of the 10–370 mg/dL range indicated excessively diluted or concentrated (in vivo) urine samples. ^b: Users of NRT products were excluded from the analysis if participants indicated “yes” to the NHANES question SMQ863, within the SMQRTU_I questionnaire set. ^c: Seven participants under the age of 17 were excluded due to the small sample size of this age group. For the user population, the steps taken to categorize daily and non-daily users have been provided in text.

Figure 1

Logarithmic distributions and correlations for urinary cotinine, trans-3′-hydroxycotinine, nicotine, and TNEs, from NHANES 2015–2016. Within each panel, the Pearson correlation coefficient is designated as the top number, and the p-value is designated as the bottom number. Pearson correlation coefficients are obtained from un-weighted, log-transformed (base 10) biomarker and TNE concentrations without adjusting for the urinary creatinine concentration. Each panel contains information for (a) combined non-user and user populations, (b) non-user population only, and (c) user population only.