Developing caffeine reduction interventions in quitting smokers

Smoking remains the leading cause of preventable death worldwide. Despite success in reducing the prevalence of smoking in high-income countries in the UK, much of this has been due to reductions in uptake among young people, rather than improvements in cessation rates in established smokers. While many smokers report wanting to quit, only a proportion of these attempt to quit, and only a minority successfully stop smoking in the long-term. Research suggests that moderate to high caffeine intake during a quit attempt may substantially reduce the likelihood of success. This is a crucial finding given that the majority of smokers also consume caffeine, and that caffeine consumption levels tend to be higher among smokers compared to non-smokers. The importance of this effect is further exemplified by the fact that caffeine intake is a modifiable factor, which individuals can control to aid quit attempts. Taken together, this indicates that caffeine consumption is critically overlooked in smoking intervention services and within smoking cessation advice.

The underlying cause of the relationship between caffeine consumption and smoking cessation appears to be (at least partially) due to cigarette smoke increasing caffeine metabolism. This means that when an individual is smoking, caffeine is broken down more quickly and there will be a lower level of caffeine in the smoker's system. However, when an individual stops, or reduces, smoking, caffeine metabolism slows down. Therefore, there will be higher levels of caffeine in the individual's system, despite the fact they haven't changed the amount of caffeine they consume. Importantly, high levels of caffeine consumption produce caffeine toxicity, an aversive state similar to nicotine withdrawal (e.g., restlessness, insomnia). As the individual hasn't changed their caffeine intake (but has reduced smoking), these effects are likely to be misinterpreted as smoking withdrawal, which in turn would increase the likelihood of relapsing to smoking.

The importance of this explanation is that caffeine intake does not have to be reduced to zero. Instead, it just needs to be reduced at the point of smoking cessation, in order that levels of caffeine do not increase to levels associated with toxicity. Previous research has investigated the impact of caffeine intake on smoking cessation and failed to find a positive effect of caffeine abstinence. However, we argue that this failure is due to a focus on caffeine abstinence rather than caffeine reduction. The reason for this is twofold: 1) total caffeine abstinence may be hard to achieve particularly when an individual is also trying to abstain from smoking; and 2) low levels of caffeine may aid a quit attempt by attenuating nicotine withdrawal.

This project will conduct a series of activities that engage with local authority Stop Smoking Services (SSS) and smokers, to develop caffeine reduction interventions for quitting smokers. This activity will include a public survey, a series of focus groups and an observational study run out of SSS. The primary aim will be to develop a caffeine reduction intervention that can be easily and cost-effectively incorporated into SSS, with minimal resource requirements. Furthermore, as many smokers quit without seeking stop-smoking support, we will explore ways to deliver this intervention directly to smokers (e.g., by developing applications that can be run on mobile platforms). The outputs from this project will include a "menu" of caffeine reduction strategies (informed by the survey and focus groups), a strategy for integration of a caffeine reduction intervention within current care in SSS, caffeine reduction intervention materials that can be used by service providers with minimal additional training, and smoker-initiated ideas for population-level delivery of caffeine reduction interventions (including design of a mobile platform application).

Observational studies have identified an inverse relationship between caffeine consumption and smoking cessation. Furthermore work from our own group using Mendelian randomisation methods indicates that this relationship is causal. As caffeine consumption is a tractable target, investigation of caffeine reduction methods and outcomes is warranted. The importance of this work is further exemplified by the fact that caffeine consumption is common among smokers and tends to be higher in smokers compared to non-smokers.

The mechanism underlying this effect seems to be, at least in part, metabolic. Cigarette smoke increases CYP1A2 activity, which is responsible for around 95% of caffeine metabolism. Thus, when an individual stops smoking, caffeine metabolism decreases, due to a loss of smoking-induced enhancement of the metabolising enzyme. This leads to a marked increase in circulating caffeine that builds up over time, despite no behavioural change in caffeine consumption.

The research showing this effect dates back several decades, and it is therefore surprising that caffeine reduction is typically lacking from stop-smoking advice. In fact, the degree of the effect (i.e., caffeine levels increasing by 250% post-quit) indicates that the lack of caffeine advice is a serious omission. One explanation for this is that subsequent research failed to show benefits of caffeine abstinence on smoking cessation. We argue that this is due to a focus on caffeine abstinence rather than caffeine reduction. This project will develop caffeine reduction interventions that can be delivered both within Stop Smoking Services and directly to quitting smokers who do not present to services (e.g., through mobile platform applications). Throughout the project we will engage with SSS and smokers, and we will conduct an observational study testing the choice and effect of different caffeine reduction strategies.

Despite a decline in smoking rates during the latter half of the last century, smoking rates have stabilised at around 20% of the UK population. However, much of this decrease has been due to reductions in smoking uptake among young people, rather than due to substantial increases in cessation among current smokers. Around half of all regular smokers will die as a direct result of their addiction and many more will suffer negative health effects due to smoking. While many smokers report wanting to quit smoking, few are able to maintain long-term smoking abstinence. There is therefore a pressing need to improve smoking cessation rates, which is particularly challenging given the chronic and severe nature of the addiction and due to the limited resources available to run Stop Smoking Services in the community.

Growing evidence indicates that failure to take account of caffeine consumption during smoking cessation is a serious omission, which is likely to be a contributing factor to poor cessation outcomes. This project will develop caffeine reduction interventions for quitting smokers. This work has substantial impact potential based on the following:

1. The reported underlying effect is large. While an individual is smoking, cigarette smoke increases the rate of caffeine metabolism. This metabolism is slowed down when an individual stops smoking, and levels of circulating caffeine can increase by 250% within a few weeks. In moderate to high caffeine consumers this is likely to lead to caffeine toxicity effects that will make it very difficult to maintain a smoking quit attempt.

2. Caffeine consumption is a tractable target. Unlike some drivers of relapse, caffeine consumption is one that is within the control of the individual and can be achieved in a number of ways. For example, opting to replace every other caffeinated drink with a decaffeinated one means individuals do not need to reduce the number of cups they consume per day, thereby requiring little change to consumption. It is also possible to develop simple, but effective, materials to support this adjunct advice within current Stop Smoking Services (SSS) that require little additionally training. Taken together, this indicates this intervention would constitute a particularly cost-effective addition to current practice.

3. Our focus is reduction rather than abstinence. The nature of the metabolic effect means that individuals do not need to quit caffeine consumption alongside smoking, which may be difficult to maintain. This means that the targeted reduction in caffeine consumption is more likely to be achievable.

We will optimise the impact potential of this work by expanding delivery of the intervention beyond SSS. This is critical as many quitting smokers do not enrol in, or do not have access to, local SSS. The simple nature of the intervention means that it can be effectively communicated and implemented without specialist involvement. This provides the opportunity for us to develop channels of intervention delivery directly to smokers, such as through online applications. This will substantially enhance the impact of this work.