Capping Nicotine in Combustibles is Bad Policy
The Center for Tobacco Products (CTP) recently announced a proposed rule that would “make cigarettes and certain other combusted tobacco products minimally or nonaddictive by limiting the level of nicotine in those products.” They propose limiting the amount of nicotine in a cigarette to no greater than 0.7 mg of nicotine per gram of tobacco. The logic behind the rule stems from the assumption that nicotine is what makes quitting cigarettes such a difficult task. Though meritorious in concept, the underlying science suggests that this move is unlikely to impact the nation’s smoking rate.
The science does not support the claim.
Very low nicotine content (VLNC) cigarettes were first promoted in 1994 to reduce the addictive level of combustible cigarettes. By limiting the amount of nicotine to 0.4-0.5 mg per cigarette, researchers believed that cigarettes would be less likely to induce addiction. Though this limit was purely theoretical, advances in agriculture biotechnology introduced VLNC cigarettes, and public health and regulatory agencies have attempted to generate sufficient evidence to pursue national limits on nicotine content.
Several studies have explored how a reduction in nicotine levels might act to decrease combustible cigarette use—and therefore addiction rates. In the most extensive study to date, researchers provided 780 subjects with cigarettes containing 15.8, 5.2, 2.4, 1.3, or 0.4 mg/g (either natural or menthol flavored) over a six week period. Subjects were provided with 25 percent more cigarettes per day (CPD) as compared to their baseline CPD. The study found that the subjects that were provided with the lower nicotine cigarettes smoked fewer CPD than those subjects with more concentrated cigarettes. This statement, though, is only technically correct. Based on the data, there was no real difference when compared to subjects’ baseline values: Subjects who used products with lower concentrations of nicotine did not increase their CPD compared to their baseline values as much as those subjects who used higher nicotine products.
Several other studies have found that lower nicotine products produce data that suggests less consumption when compared to higher nicotine products, but that use was not reduced to below baseline levels. This indicates that the use of these products do not reduce overall smoking behavior. Additionally, the studies also reported large amounts of non-compliance, in which subjects augmented smoking cigarettes received for free during the study with self-acquired non-VLNC cigarettes of their preferred brand.
But it might work…right?
There has been a single study that showed a reduction in smoking. This study assessed how the use of non-combustible nicotine delivery products along with VLNC regulation might impact overall product use behavior by recruiting 136 subjects, who were randomized into one of three groups. The first (VLNC1, n=53) were subjects provided with 1.3 mg/g VLNC cigarettes as well as given access to other non-cigarette combustibles (i.e. cigars), non-combustibles, and nicotine (medicinal) products. The second experimental group (VLNC2, n=56) were provided with the same VLNC cigarettes but were only allowed to supplement use with non-combusted products. The third group was provided with normal nicotine content (NNC, n=27) cigarettes and they were allowed access to non-cigarette combusted and non-combusted nicotine products. Following a 2-week assessment to establish baseline use, subjects were randomized into groups. Subjects were allowed to test their assigned product and then use points (25 points = $25 worth of product) to purchase supplementary tobacco/nicotine products. Subjects also received cigarettes at 150 percent the number of their baseline CPD. The subjects had to decide to supplement their usage with other products (products would be significantly discounted and unused points lost value over time) or keep points that would be “cashed out” for real currency at the end of the study. Reductions in total study CPD occurred in both of the VLNC groups.
The data suggest that VLNC can work to reduce total cigarette use, but only if alternative sources of nicotine, such as e-cigarettes or nicotine pouches, are available. Based on these data, the authors suggested that one way to mitigate concerns about the potential unintended consequences of instituting a VLNC standard as part of regulatory control is to support and educate adult tobacco users on the importance of potentially including non-combustible products as part of their overall tobacco use reduction strategy.
There is not sufficient research on the actual nicotine level proposed.
For reasons undisclosed in the proposed rule, the CTP decided that the maximum level of nicotine allowed would be 0.7 mg/g. This is confusing because none of the current research evaluated that level of nicotine. In fact, the levels that were available in research cigarettes were higher and lower than 0.7 mg/g. The CTP has long held manufacturers to a standard that requires that the science used to support applications for selling tobacco and nicotine products be based on the product they intend to sell, with data generated by a sample of research subjects that mirror the smoking population. But the CTP does not apply that same standard to their own rule.
The absence of following the scientific process for supporting public health claims.
Since 2010, there have been only a handful of clinical trials that have investigated how the VLNC strategy may impact the use of combustible cigarettes by adult consumers of tobacco products. Many of these investigations were hampered by methodological shortcomings, making conclusions problematic. Using these studies to predict how the smoking population will respond to the proposed nicotine standards would be problematic. Not only were the studies too underpowered to be relevant estimators beyond pilot work, but they also focused on investigational products that were not accessible to consumers and did not assess how lower nicotine levels might affect use.
In order for the CTP to claim that VLNCs would reduce the addictive nature of cigarettes—that they would act as a cessation tool—the level of research required to support such a claim must reach the criteria for products evaluated by the Center for Drug Evaluation and Research (CDER). At this point, the data that currently exists does not meet this standard.
The effects of non-compliance at the population level.
The overwhelming concern is the quality of evidence gathered through studies where it is estimated that over 70 percent of the subjects are non-compliant. Such non-compliance has led to attempts to both evaluate the rate of non-compliance and to resolve the non-compliance issue in the dataset to resurrect the usefulness of the study itself. Many investigators try to overlook this as a major concern, suggesting that the amount of study cigarettes used was enough to provide an estimate of what might be expected if VLNC cigarettes were available in the marketplace. However, currently available VLNC products are not quality products that research participants will exclusively use, even when provided for free. Furthermore, if adult consumers are provided with currently available VLNC products, data suggests that there is a high likelihood that they will seek out normal nicotine cigarettes through alternative means (such as illicit sources).
Summary
Instead of capping nicotine levels, an alternative solution may involve allowing the industry to invest resources into next-generation, non-combustible products that are attractive to those who smoke. Developing products that provide a real choice in format and empower individuals to transition to reduced-risk products may lead to a more impactful change in reducing smoking-related morbidity and mortality. The CTP should continue evaluating—and approving—alternative nicotine products while providing transparent and science-based information to those who smoke to help them make the switch.