Nicotine is often discussed mainly as the chemical that makes cigarettes and other tobacco products addictive.
But a major scientific review argues that nicotine itself can directly harm the heart and blood vessels, even when it is delivered without burning tobacco.
The findings help explain why newer nicotine products may reduce some risks compared with cigarettes without becoming harmless.
The review was published in Nature Reviews Cardiology and brought together evidence from laboratory studies, biological measurements, animal research and studies involving people.
Researchers examined the effects of nicotine across cigarettes, waterpipes, heated tobacco, e-cigarettes and oral nicotine products. Their goal was to understand what nicotine itself does to the cardiovascular system.
Tobacco remains a huge global health problem. The review notes that more than one billion people smoked tobacco in 2023, with millions of deaths linked to direct smoking and secondhand smoke. Cardiovascular disease, including heart attacks and strokes, accounts for a large share of tobacco-related deaths.
Cigarette smoke contains thousands of chemicals, so scientists have long tried to separate the effects of nicotine from the damage caused by smoke and combustion. Burning tobacco produces many toxic substances that can injure blood vessels and lungs. This has sometimes led people to assume that nicotine is mainly an addiction problem rather than a cardiovascular toxin.
The new review challenges that simple picture. Lead author Professor Thomas Münzel of University Medical Center Mainz in Germany said the evidence shows that nicotine can activate receptors on cells lining blood vessels. This begins a chain of biological changes that makes the vessels less able to relax normally.
Healthy arteries are not just passive tubes carrying blood. Their inner lining helps control whether vessels widen or narrow and also helps prevent unwanted blood clots. Damage to this protective lining is considered an early step in the development of atherosclerosis, the gradual buildup of harmful deposits inside arteries.
According to the review, nicotine interferes with chemicals that normally help blood vessels stay open. It reduces the action of prostacyclin, which helps vessels relax and also discourages excessive clotting. At the same time, nicotine promotes endothelin-1, a substance that strongly encourages blood vessels to tighten.
Nicotine may also attack blood vessels through a second route. It can act directly on the muscle cells surrounding arteries and alter the signals that control contraction. The result is a blood vessel that is more likely to tighten and less able to relax.
These changes can raise the workload on the cardiovascular system. Narrower vessels can contribute to higher blood pressure, while damaged vessel walls can become more inflamed and more likely to support clot formation. Over many years, these processes may help create conditions that lead to heart disease.
Atherosclerosis develops when fatty material, cholesterol, inflammatory cells and other substances build up in artery walls. These deposits are known as plaques. If a plaque becomes unstable and breaks open, a blood clot can suddenly form and block blood flow.
When this blockage occurs in an artery supplying the heart, it can cause a heart attack. If a clot blocks blood flow to part of the brain, it can cause an ischemic stroke. The review traces how nicotine-related changes in blood vessels could contribute to this long chain of events.
The authors also compared different types of nicotine products. They concluded that products involving combustion, including cigarettes and waterpipes, produce the greatest cardiovascular harm. This makes sense because users are exposed not only to nicotine but also to the many toxic chemicals created when tobacco burns.
Heated tobacco products were placed below combustible products in the review’s overall hierarchy of harm, followed by aerosol products such as e-cigarettes and then oral nicotine products. The researchers stressed that lower risk does not mean no risk. Their analysis describes a continuum, with avoiding nicotine and tobacco exposure carrying the lowest risk.
This distinction is important for people who smoke. Switching completely away from combustible cigarettes may reduce exposure to many dangerous products of burning tobacco. However, the review argues that continuing to use nicotine can still have biological effects on the cardiovascular system.
The authors are particularly concerned about young people who begin using e-cigarettes or nicotine pouches without previously smoking. In this situation, a product described as less harmful than cigarettes can still introduce nicotine dependence and long-term exposure where none existed before. Nicotine can make repeated use difficult to stop.
The review also questions comparisons between nicotine and everyday stimulants such as caffeine. Although both can affect alertness and the cardiovascular system, nicotine has a strong ability to create dependence. Regular exposure can lead users to continue taking it even when they want to quit.
Professor Filippo Crea, one of the authors, said the combined evidence indicates that nicotine contributes to dysfunction of the blood vessel lining.
The researchers connect this early damage with later risks including atherosclerosis, high blood pressure and heart failure. They argue that regulation should therefore consider nicotine itself rather than treating every product as an entirely separate issue.
The authors support stronger efforts to prevent young people from starting nicotine use and greater access to proven help for people trying to quit. They also discuss policies such as taxation and restrictions on flavors. Their broader argument is that public messages should clearly distinguish between reduced harm and absence of harm.
There are important points to keep in mind when interpreting the review. It brings together many types of evidence rather than reporting one new randomized clinical trial, and the strength of evidence is not identical for every product or every cardiovascular outcome.
Long-term data for newer products are also naturally more limited because they have not been widely used for as many decades as cigarettes.
Another important issue is that nicotine replacement products used for smoking cessation have a different purpose and exposure pattern from recreational nicotine use. For someone who smokes cigarettes, medically supported quitting strategies can reduce the much greater danger associated with continued smoking.
People should not avoid evidence-based smoking cessation treatment because they interpret the review as saying that every nicotine exposure carries the same level of risk.
The strongest message from the review is therefore about relative rather than identical harm. Cigarettes remain especially dangerous because combustion adds many toxins on top of nicotine exposure, while noncombustible products may reduce some of that harm.
But the biological evidence reviewed by the researchers suggests that nicotine itself should not be treated as harmless to the cardiovascular system.
Overall, the review provides a useful explanation for why cardiovascular risk does not disappear simply when smoke disappears.
Its strength comes from connecting molecular and laboratory findings with evidence from multiple nicotine products and human studies. More long-term research is needed for newer products, but the findings support avoiding nicotine initiation and helping current smokers move toward complete cessation.
Source: University Medical Center Mainz
