A cigarette, an e-cigarette and a nicotine pouch look very different, but they can all deliver the same addictive chemical: nicotine.
A wide-ranging scientific review now suggests that this shared ingredient has important effects on the cardiovascular system. Nicotine may damage the normal function of blood vessels through several biological pathways, regardless of how it enters the body.
The review, published in Nature Reviews Cardiology, was led by Professor Thomas Münzel of University Medical Center Mainz in Germany with an international team of cardiovascular experts.
The authors examined evidence from studies of cells, animals, biological markers and patients. They also compared major categories of nicotine-containing products instead of studying each one in isolation.
This question has become more important as nicotine products have changed. Traditional cigarettes are still widely used, but e-cigarettes, heated tobacco and oral nicotine pouches have expanded the ways people can consume nicotine. Some of these products have been promoted or perceived as safer alternatives because they do not burn tobacco.
Burning tobacco is unquestionably a major source of harm. Combustion creates a complex mixture of toxic chemicals and tiny particles that can damage the lungs, blood vessels and other organs. Removing combustion can therefore reduce exposure to many dangerous substances.
But reduced exposure to smoke does not automatically make nicotine harmless. The new review focuses on what happens after nicotine reaches the bloodstream and interacts with cells in blood vessel walls. The authors describe several changes that may push the cardiovascular system toward vessel narrowing, inflammation and clotting.
The inner surface of a blood vessel is covered by a very thin layer of cells that helps keep circulation working smoothly. These cells release signals that tell the vessel when to widen and when to tighten. They also help control inflammation and prevent blood from clotting when no clot is needed.
Nicotine can disturb this protective system. According to the review, it activates receptors on blood vessel cells and interferes with the processes that normally allow arteries to relax. This can leave the vessel lining less able to perform its protective role.
One effect involves prostacyclin, a natural substance that helps blood vessels widen and makes platelets less likely to clump together. The review reports that nicotine can suppress this protective signal. At the same time, it can increase the release of endothelin-1, which has the opposite effect and strongly narrows blood vessels.
The authors describe another route that does not depend on damage to the vessel lining. Nicotine can directly influence the smooth muscle that surrounds arteries. By changing the way these muscle cells handle electrical and calcium signals, nicotine can encourage the vessel to contract.
Professor Münzel described these as two separate routes leading toward a similar result. The vessel becomes more likely to constrict and less able to relax. Conditions may also become more favorable for inflammation and unwanted clot formation.
These effects matter because cardiovascular disease often develops over many years. Repeated injury to blood vessels can contribute to atherosclerosis, in which fatty and inflammatory material accumulates within artery walls. As plaques grow, arteries may become narrower and blood flow can become more difficult.
The most dangerous moment can occur when an unstable plaque suddenly ruptures. The body treats the rupture like an injury and forms a clot over it. If that clot closes an important artery, the result may be a heart attack or stroke.
The review argues that nicotine can contribute to several steps along this pathway. It is not the only cause, and smoking adds many other damaging chemicals, but nicotine appears to be an active participant rather than simply the substance that keeps people addicted. This helps explain why removing smoke may not remove all cardiovascular risk.
When the researchers compared products, combustible tobacco such as cigarettes and waterpipes ranked as the most harmful. Heated tobacco products came next, followed by aerosol products such as e-cigarettes and then oral nicotine products. Complete avoidance of tobacco and nicotine was considered the lowest-risk option.
This ranking should not be misunderstood as saying that every product is equally dangerous. A person who switches completely from cigarettes to a noncombustible alternative may reduce exposure to many combustion-related toxins. The review’s point is that a lower-risk product can still carry risk, particularly because nicotine itself remains biologically active.
This is also different from the situation of a person who has never smoked but begins using nicotine through vaping or pouches. For that person, there is no smoking-related harm to reduce. Instead, the new product creates exposure to nicotine and the possibility of dependence.
Dependence is one of the review’s major concerns. Nicotine changes brain reward systems in ways that encourage repeated use and make stopping difficult. For young users, starting early could potentially lead to many years of exposure.
The authors therefore argue that health regulation should focus more clearly on nicotine across product categories. They support measures aimed at preventing initiation, particularly among young people, while also helping existing users quit. The review discusses approaches including taxation, restrictions on attractive flavors and evidence-based cessation support.
From a scientific perspective, one strength of the review is its attempt to connect different levels of evidence. Laboratory studies can show what nicotine does to individual cells, while clinical and biomarker studies can show whether similar changes appear in people. Looking across these layers can provide a fuller picture than relying on one type of research alone.
There are limitations, however. A review depends on the quality of the studies available, and long-term evidence for newer nicotine products remains less complete than the decades of data available for cigarettes. Cardiovascular risk is also influenced by dose, frequency, years of use and whether a person uses several products at the same time.
It is also important not to confuse recreational nicotine use with medically supervised smoking cessation. Nicotine replacement therapies can be used for a limited period to help people stop smoking, and continued cigarette smoking carries major established risks.
Anyone trying to quit should discuss appropriate evidence-based options with a health professional rather than abandoning treatment because nicotine itself is not risk-free.
The review’s central conclusion is straightforward: smoke is not the only part of tobacco and nicotine use that matters to the heart. Combustion makes cigarettes particularly dangerous, but nicotine can independently interfere with the normal behavior of blood vessels. That means products can differ greatly in harm without any nicotine product becoming completely harmless.
Overall, the research strengthens the case for preventing nicotine use among people who do not already use it while continuing to support smokers who want to quit. The precise long-term risks of newer products will become clearer as more data accumulate. For now, the evidence suggests that the safest cardiovascular choice is to avoid chronic nicotine exposure altogether.
Source: University Medical Center Mainz.
