What is nicotine's role in tobacco-related diseases?

Smoking causes manifold health issues causing cardiovascular and respiratory diseases. Moreover, smoking significantly increases the risk for many cancers, the most obvious and prominent example is lung cancer. The WHO estimates that more than 8 million people die prematurely yearly from tobacco use. EIGHT MILLION.... This is a huge death toll. New nicotine and tobacco-derived products may substantially reduce this number if a substantial number of smokers switches to those products in case that they are not able to quit completely.
This case is called tobacco harm reduction and the question is to which extent do these products reduce the risk of the consumers to develop one of the illnesses related to smoking...

In order to address this question properly, it is of paramount importance to understand nicotine's role in these diseases and its potential toxicity. As Prof. Russell stated already 33 years ago, people smoke for the nicotine, but die from the tar. That means that while nicotine is the addictive compound smokers crave for, they are exposed to 1000s of chemicals present in smoke and many of them are toxic and/or carcinogenic. Still, several studies seem to show that nicotine causes many of the diseases related to smoking.

We addressed the question "What is nicotine's role in human health?" in an extensive literature review published in Contributions to Tobacco & Nicotine Research.

The review included around 500 peer-reviewed articles and we tried to rank nicotine's role in the described health effects based on the outcome of the studies for the different disease states such as cardiovascular, respiratory, oral diseases and cancer progression. It turned out that most negative impacts are mainly associated with the toxic smoke constituents rather than nicotine itself. Many studies, suggesting a negative impact of nicotine itself in users of alternative products do not properly take into account the smoking history of the subjects. And this is a big problem which can lead to false conclusions.
Let's take a simple example to illustrate the issue. If I calculate the cancer risk in vapers (users of electronic cigarettes) without taking into account their smoking history, I can come to the conclusion that vaping causes lung cancer. When I discriminate by years of smoking prior to the initiation of vaping, I get a different picture.
The role of nicotine suffers from such shortcomings in many studies.

In the majority of human studies, the study design does not allow to deduce the role of nicotine in the observed biological endpoints, leaving open the question, whether nicotine is at least partly responsible for the observed effects or not involved at all.
In contrast, nicotine has proven beneficial for several neuronal diseases such as dementia and Alzheimer! Clearly, we need to accurately differentiate the included subjects based on their smoking history to get meaningful data, which is one of the key take home messages from our review.

What can we do to clarify the risk from nicotine use apart from smoking?

One option is just to wait. Time will tell... Once a large number of vapers and users of other new product categories like nicotine pouches who consumed those products over a longer time period and had not smoked in their lifetime is available the epidemiology will show the effects on public health.

But we do not want to wait so long! Is there no other way?

Here, ABF's research comes into play! Some endogenous compounds present in our body whose concentrations are significantly altered in disease states. Ideally, such so-called biomarkers of potential harm show changes before the disease manifests. They can serve as early predictors and improve our understanding of the harmful effects of the new products.
Research on biomarkers of potential harm includes non-targeted analysis from controlled and longitudinal studies. Their identification and implementation in clinical studies can help us to better understand the real burden from nicotine and the impact of tobacco harm reduction on public health. We are committed to contribute our part in this research question.

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