Immediate nicotine reduction best at cutting biomarkers of smoke exposure
The immediate reduction of cigarette nicotine content results in greater improvements in levels of smoke exposure biomarkers than gradual reduction, though withdrawal symptoms are stronger, according to a recent study.
The double-blind, randomized, parallel study included 1,250 participants, who were randomized to one of three 20-week interventions delivered after 2 weeks of baseline smoking: immediate reduction of nicotine to 0.4 mg/g tobacco (n=503; mean age 45.5±13.9 years; 46 percent female), gradual reduction to 0.4 mg/g tobacco (n=498; mean age 44.7±12.9 years; 42 percent female) or nicotine maintenance at 15.5 mg/g tobacco (control; n=249; mean age 45.0±13.4 years; 43 percent female).
After 20 weeks, participants in the immediate vs gradual reduction group had significantly lower mean breath carbon monoxide levels (16.17 vs 20.06 ppm; adjusted mean difference [MD], –4.06 ppm; 95 percent CI, –4.89 to –3.23; p<0.0055). [JAMA 2018;329:880-891]
The same was true for other smoke exposure biomarkers: urine 3-hydroxypropylmercapturic acid (3-HPMA; adjusted ratio of geometric means [RGM], 0.83; 0.77–0.88; p<0.0055) and urine phenanthrene tetraol (Phe-T; adjusted RGM, 0.88; 0.83–0.93; p<0.0055).
The 20-week intervention also resulted in significant reductions relative to the control group (CO: adjusted MR, –3.38; –4.40 to –2.36; p<0.0055; 3-HPMA: adjusted RGM, 0.81; 0.75–0.88; p<0.0055; PheT: adjusted RGM, 0.86; 081–0.92; p<0.0055). No significant differences were observed between the control and gradual reduction groups.
Immediate reduction of cigarette nicotine also had a significant effect on smoking habits. Relative to the gradual reduction (adjusted MD, –5.18; –5.97 to –4.39; p<0.00057) and control (adjusted MD, –5.47; –6.44 to –4.50; p<0.00057) groups, significantly less cigarettes per day were recorded for the immediate reduction group.
Participants who received the immediate reduction intervention likewise demonstrated significantly lower nicotine dependence, as measured by the Fagerström Test (adjusted MD, –0.99; –1.75 to –1.12; p<0.00057), and significantly more cigarette-free days (incidence rate ratio [IRR], 3.57; 2.34–5.43; p<0.00057) compared with the gradual reduction intervention.
“[T]he results demonstrated that with immediate nicotine reduction, the toxicant exposure reduction or potential health benefits could be realized sooner than gradual nicotine reduction,” researchers explained.
“Although the actual reduction in mortality and morbidity as a result of the reduced cumulative exposure in the immediate compared with the gradual nicotine reduction group is unknown, dose-response relationships have been observed between CPD and level of smoke exposure with risk for tobacco-related disease,” they added.
However, researchers noted that the immediate reduction in cigarette nicotine was not without its drawbacks. For instance, withdrawal symptoms, measured using the Minnesota Nicotine Withdrawal Scale, were stronger for 1 week in the immediate vs gradual reduction groups (adjusted MD, 2.21; 1.62–2.79; p<0.00057).
Moreover, participants who received the immediate reduction intervention were significantly less compliant than the gradual reduction group, using more nonstudy cigarettes (adjusted MD, 1.58; 1.12–2.04; p<0.00057).
“Compared with gradual nicotine reduction, immediate reduction resulted in more dropouts and use of nonstudy cigarettes, possibly reflecting an attempt to reduce withdrawal symptoms and the lack of satisfaction from cigarettes,” researchers said, suggesting that smokers would tend to seek out alternative nicotine sources.
“The availability of alternative regulated sources of nicotine that have been proven to be less harmful, along with access to smoking cessation treatments through physicians and other sources and a strong postmarketing surveillance system, would likely minimize demand for illicit cigarettes,” they added.