Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers

Background: Oral nicotine pouches (NPs) are smokeless, tobacco-free products that have a potential role in tobacco harm reduction strategies.Methods: In a cross-sectional study in Sweden/Denmark, several recognised biomarkers of potential harm (BoPHs) linked to smoking-related diseases/their initiating biological processes, and biomarkers of exposure (BoEs) to tobacco/tobacco smoke toxicants were compared among exclusive adult users of Velo NPs and current/former/never smokers. Over 24 h, participants used their usual product (Velo NP or cigarette) as normal, and BoEs/BoPHs were assessed via blood/24-h urine/exhaled breath/physiological assessments.Results: Among the primary endpoints, total NNAL (16.9 +/- 29.47 vs 187.4 +/- 228.93 pg/24 h), white blood cell count (5.59 +/- 1.223 vs 6.90 +/- 1.758 x 10(9)/L), and COHb (4.36 +/- 0.525 vs 8.03 +/- 2.173% saturation) were significantly lower among Velo users than among smokers (91%, 19% and 46% lower, respectively, all P < 0.0001), while fractional exhaled NO, previously shown to be lower in smokers, was significantly higher (23.18 +/- 17.909 vs 11.20 +/- 6.980 ppb) among Velo users (107% higher, P < 0.0001). Furthermore, sICAM-1 tended to be lower (185.9 +/- 42.88 vs 204.5 +/- 64.85 ng/mL) among Velo users than smokers (9% lower). Several secondary endpoints, including six BoEs (3-HPMA (246.7 +/- 91.07 vs 1165.7 +/- 718.35 mu g/24 h), 3-OH-B[a]P (82.4 +/- 217.58 vs 258.3 +/- 190.20 pg/24 h), HMPMA (135.1 +/- 77.85 vs 368.8 +/- 183.15 mu g/24 h), MHBMA (0.22 +/- 0.166 vs 3.39 +/- 2.943 mu g/24 h), S-PMA (0.10 +/- 0.059 vs 3.53 +/- 2.736 mu g/24 h) and total NNN (7.5 +/- 24.84 vs 9.7 +/- 5.93 ng/24 h)), were significantly lower among Velo users (78.8%, 68.1%, 63.4%, 93.5%, 97.2% and 22.7% lower, respectively, P < 0.0001-0.0011), while total nicotine equivalents was significantly higher among Velo users (22.6 +/- 12.69 vs 12.1 +/- 7.92 mg/24 h, P < 0.0001), although Velo user levels are comparable to those previously reported among oral tobacco users, and Velo user and smoker mean levels were similar in Denmark.Conclusion: As compared with smokers, exclusive users of Velo NPs have significantly less exposure to tobacco toxicants and more favourable BoPHs associated with initiating biological processes of smoking-related diseases.International Standard Registered Clinical Trial number: ISRCTN16988167

Automated summary

Exclusive users of Velo NPs have significantly less exposure to tobacco toxicants and more favorable biomarkers associated with smoking-related diseases compared to smokers.