Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Immediate vs Gradual Nicotine Reduction in Cigarettes

JAMA; ePub 2018 Sep 4; Hatsukami, et al

Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction, a recent study found. The double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. The objective was to determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. The primary outcome was between-group differences in 3 co-primary biomarkers of smoke toxicant exposure. Researchers found:

  • Among 1,250 randomized participants (mean age 45 years; 445 women), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for carbon monoxide (CO).
  • Immediate compared with gradual reduction to very low nicotine content cigarettes or with a control smoking group significantly reduced exposure to CO, acrolein, and phenanthrene tetraol.
  • There were no significant differences between the gradual and control groups for CO.


Hatsukami DK, Luo X, Jensen JA, et al. Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure. A randomized clinical trial. JAMA. 2018;320(9):880–891. doi:10.1001/jama.2018.11473.

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