Effects of immediate versus gradual nicotine reduction in cigarettes on biomarkers of biological effects.

Abstract

AIM\nA previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects.\n\n\nDESIGN\nThree-arm, randomized controlled trial.\n\n\nSETTING\nTen United States academic institutional sites.\n\n\nPARTICIPANTS\nDaily smokers uninterested in quitting smoking with a mean (SD) age of 45.1 (13.4) years and smoking 17.1 (8.5) cigarettes/day; 43.9% (549/1250) female; 60.6% (758/1250) white ethnicity.\n\n\nINTERVENTIONS\n1) Smoking cigarettes where nicotine content was immediately reduced to very low levels (n=503); 2) smoking cigarettes where nicotine content was gradually reduced, with dose changes occurring monthly (n=498); 3) continued smoking with normal nicotine content cigarettes (n=249).\n\n\nMEASUREMENTS\nSmokers were assessed at baseline, while smoking their usual brand cigarettes, and again at 4, 8, 12, 16 and 20 weeks. Outcomes were areas under the concentration time curve (AUC) for the period of study of biomarkers of inflammation, oxidative stress and hematological parameters.\n\n\nFINDINGS\nNo consistent significant differences were observed across groups (Bayes factors showing data to be insensitive), with the only exception being red blood cell size variability, which was observed to be lower in the immediate vs. gradual nicotine reduction (mean difference -0.11; 95% CI -0.18, -0.04, p=0.004) and normal nicotine control groups (mean difference -0.15, 95% CI -0.23, -0.06, p=0.001).\n\n\nCONCLUSION\nIt remains unclear whether switching to very low nicotine cigarettes leads to a short-term reduction in biomarkers of tobacco-related harm.