To our knowledge, this is the first study to characterize nicotine and carcinogen exposures and cardiovascular responses to forced switching of smokers to progressively lower nicotine yield commercial cigarettes. Numerous other studies, both cross-sectional and experimental forced switching studies, have found that smokers compensate completely or nearly completely for commercial low yield cigarettes with nicotine yields of ≥0.6 mg (6
). Correspondingly, we found that plasma cotinine concentrations, blood carbon monoxide, NNAL, and PAH metabolite excretion changed very little from baseline to the 0.4 mg nicotine yield level (study week 4).
While smoking the 0.2 and 0.1 mg nicotine yield cigarettes, commonly described as ultralow yield cigarettes, there was a significant reduction in nicotine intake as well as in carbon monoxide, NNAL, and PAH exposure. There was also a 17% average increase in cigarettes smoked per day when smoking the lowest yield cigarette, although this change was not statistically significant. The reduction in nicotine intake despite smoking more cigarettes per day has been reported previously in both short-term switching studies and cross-sectional studies of smokes of ultralow yield cigarettes in the 0.1 to 0.2 nicotine category as well (7
). One short-term switching study showed a reduction in carcinogen exposure as indicated by significantly reduced mutagenic activity of the urine after switching from regular to 0.1 mg nicotine cigarettes (8
). A recent cross-sectional study of nicotine and carcinogen exposure with different yield cigarettes by Hecht et al. did not find lower exposure with ultralight cigarettes (25
). However, in the Hecht et al. study, the ultralight cigarette category included brands with tar yields of ≤6.5 mg tar, which overlaps with the 0.4 and 0.6 mg nicotine cigarettes in our study, for which there was full compensation. It is unclear in the Hecht et al. study how many subjects, if any, smoked cigarettes with 0.1 or 0.2 mg nicotine yields.
We observed that after completing a commercial low yield tapering regimen that includes ultralow yield cigarettes, 4 weeks later, smokers were, on average, smoking fewer cigarettes per day and had lower dependence ratings, suggesting that the level of dependence had decreased compared with entering into the study. The findings that self-efficacy ratings were higher at the end of tapering and that the Fagerström Test for Nicotine Dependence was lower at week 10 compared with baseline also supports the idea that the level of dependence had decreased during the course of the study. The decrease in dependence observed in our study might be due to reduced nicotine exposure but could also be due to participation in an intensive research study. Furthermore, it is unknown whether a change in dependence measured in the present short-term tapering study would persist after the end of the study.
Comparison of the data from this study with that of our previously published study of progressive reduction in nicotine content of cigarettes is informative. The RNC cigarettes used in our previously published study are not commercially available but were manufactured specifically for research purposes (5
). RNC yield cigarettes are low yield because nicotine has been extracted from the tobacco, but other characteristics of the different yield cigarettes, including tar and carbon monoxide emissions, are similar for all yield levels. In contrast, the commercial low yield cigarettes used in the present study are low yield because of engineering characteristics, particularly paper and filter ventilation (26
). The nicotine content of the tobacco in commercial low yield cigarettes is comparable with that of higher yield cigarettes (27
). For the most popular low yield cigarette brands (yields of ≥0.6 mg nicotine), it is quite easy for the smoker to obtain plenty of nicotine. By puffing more intensively and/or blocking ventilation holes with fingers or lips and/or by taking more puffs per cigarette, nicotine and tar intake is substantially increased above standard machine test values (6
). For ultralow yield cigarettes in the 0.1 to 0.2 mg nicotine range, there is considerable compensation, but ventilation is so extensive that, on average, smokers are not able to fully compensate. The present and prior studies indicate that nicotine and carcinogen exposure is reduced by ~30% to 40% while smoking 0.1 mg nicotine cigarettes compared with higher yield cigarettes (7
). It should be noted that the market share of ultralow yield cigarettes with nicotine yields of 0.1 or 0.2 mg nicotine is very small (<1%), presumably reflecting that fact that nicotine delivery from these cigarette is less than desired for most smokers.
The comparison of biochemical changes with the two different types of cigarettes illustrates these differences. Cotinine levels fell progressively in relation to the decline in nicotine content with RNC cigarette tapering (16
) but declined only for the lowest two yields for the commercial low yield cigarettes. Carbon monoxide and PAH exposures and cardiovascular biomarkers did not change over the course of tapering of RNC cigarettes despite a decline in nicotine intake, consistent with the characteristics that carbon monoxide and tar emissions are similar for cigarettes across all nicotine levels. In contrast, for commercial low yield cigarettes, nicotine, carbon monoxide, and PAH exposures declined together at the lowest yield levels, consistent with the effects of extensive ventilation affecting all smoke constituents similarly.
Although RNC cigarettes have not been available in the past, the progressive reduction of nicotine yield of commercial cigarettes was studied as a possible approach to smoking cessation treatment many years ago (9
). The gradual and progressive reduction of yields was termed “nicotine fading.” Typical nicotine fading schedules involved reducing the nicotine yield of commercial cigarette brands by 30%, 60%, and 90%, on a weekly basis, and subjects were asked to monitor their “daily nicotine intake,” computed as the product of nicotine yield and cigarettes smoked that day (9
). The early trials of nicotine fading with small numbers of subjects seemed promising (9
), but later larger clinical trials found no benefit of brand fading in promoting quitting (11
The present study would be equivalent to reducing machine-determined nicotine yields, on average, by 10%, 40%, 60%, 80%, and 90% at weekly intervals. Measurement of nicotine intake using plasma cotinine concentrations indicated that actual daily nicotine intake was unchanged from baseline to the 60% reduction stage but decreased, on average, 40% when nominal nicotine yields were reduced by 90%. Thus, the 30% and 60% reduction stages described in the published nicotine fading trials would not be expected to be associated with a significant decline in nicotine exposure, whereas the 90% reduction levels would be expected to be associated with a significant reduction in nicotine intake. The present study, which included tapering by 80% and 90% of initial nicotine yield in the last 2 weeks, did seem to lower the level of nicotine dependence. Whether a more gradual reduction and the inclusion of more ultralow yield cigarette yield levels might translate into a better quitting outcome in nicotine fading procedures is unknown.
RNC cigarettes deliver less nicotine than regular cigarettes, but other components of the smoke are the same; therefore, much of the sensory sensations of smoking regular cigarettes are still present. In contrast, commercial ultralow yield cigarettes are highly ventilated, so the smoke is more dilute and sensory effects are quite different from those of regular cigarettes. Whether the lesser sensory stimulation associated with highly ventilated ultralow yield cigarettes would be as effective as that of RNC cigarettes in reducing tobacco withdrawal symptoms and in aiding smoking cessation is unknown.
As was the case with RNC cigarette tapering, we found no evidence of adverse changes in the cardiovascular biomarkers that we measured (primarily markers of inflammation) to suggest an increased cardiovascular risk with commercial low yield cigarette tapering.
Our study has several limitations. The number of subjects was small, so the power to detect modest changes is limited. Our subjects were more highly educated than the average smoker, limiting the generalizability of our findings with respect to the typical smoker. Compliance with smoking of low yield cigarettes could not be proven, but the decline in biochemical exposure when smoking the lowest yield cigarette brands suggests that subjects were for the most part compliant. It is possible that the demand characteristics of participating in a research study produced different smoking behavior with respect to the ultralow yield cigarettes than would have been observed without the implicit demands imposed by participating in a research study. That is, subjects may have felt that they could not engage in strategies to increase the nicotine yield of the ultralow yield cigarettes (such as squeezing the filter to block ventilation) without biasing the results of the study. Subjects received free cigarettes during this trial, and the period of tapering was relatively brief. It is unclear how smokers would respond to having to pay for cigarettes that were not as satisfying as the usual brand. Thus, further work will be needed to determine whether the results of this study generalize to smoking in the natural environment.
Another methodologic concern is the lack of a control group of smokers smoking cigarettes of yields similar to their usual brands who are exposed to the same experimental procedures. A control group was not included because the aim of the study was primarily to simulate a regulatory policy that might mandate progressive reductions in cigarette yields. It was not intended to be a study of low yield cigarettes as an intervention to promote smoking cessation. However, there are several reasons to believe that our results were not due to the study procedures per se. (a) Cigarette consumption remained stable or increased over the course of yield tapering. Despite relatively stable cigarette consumption, actual exposures to various tobacco smoke toxins decreased substantially. If the study procedures affected smoking behavior, one would expect cigarette consumption to decrease (reflecting health concerns) and one would not expect a marked decrease in chemical exposures per cigarette smoked. (b) We recently published another study with a similar research design, in which subjects smoked cigarettes with progressive lower nicotine content but with unchanged yields of other tobacco smoke toxins. In that study, there was the expected decrease in nicotine levels, but no change in carbon monoxide or PAH levels, indicating that the study procedure did not affect the intensity that each cigarette was smoked. (c) Our data are entirely consistent with cross-sectional population studies and experimental switching studies of commercial cigarettes of differing yields as mentioned previously. These prior studies provide external validity to our findings.
The conclusions of our study are as follows. As has been shown in many other studies, we found that forced switching from regular cigarettes to popular low yield cigarettes with machine-determined yields of ≥0.6 mg nicotine is associated with complete or nearly complete compensation, such that there is no reduction in exposure to nicotine or tobacco smoke toxins. When switching to ultralow yield cigarettes in the 0.1 to 0.2 mg nicotine yield range, exposure to nicotine and tobacco smoke toxins are substantially decreased. It is unknown whether this extent of reduction of tobacco smoke toxins would have any beneficial effect on health. Epidemiologic studies of low yield cigarettes, in general, have shown no reduction in health risk compared with higher yield cigarettes, but these studies included very few smokers of cigarettes that correspond with our two lowest yield brands (28
). We also found that tapering down to ultralow yield cigarettes may have reduced the level of nicotine dependence. Our experimental trial with a relatively small group of smokers does not establish that ultralow yield cigarettes are less addictive and less hazardous or that switching to ultralow yield cigarettes leads to a meaningful lower level of toxicant exposure. However, the possibility that gradual tapering of smokers from regular to ultralow nicotine yield commercial cigarettes might facilitate smoking cessation is suggested by our research and warrants consideration for future research, particularly larger clinical trials of smokers, especially those who are not interested in standard smoking cessation treatments, in more real-world situations.