Vaping, nicotine and the hierarchy of harm

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Despite smoking’s waning popularity, an average of 61,439 people died from smoking-attributable causes each year in England between 2022 and 2024, according to the Office for Health Improvement and Disparities. Yet only 6.4% of smokers in England were referred to stop-smoking services during the year ending March 2025.

Fortunately, vaping helps some smokers quit. “We have very strong evidence that regulated nicotine e-cigarettes are substantially less harmful than smoking,” says Dr Jamie Hartmann-Boyce, University of Massachusetts Amherst and co-author of a new Cochrane review.¹ “Based on the consistency of the findings, it is clear that they are a proven and viable option for people wishing to quit traditional cigarettes.”

The review of 80 RCTs involving 29,861 participants found that between 8-10% of people using nicotine e-cigarettes to stop smoking may quit for at least six months. This compares with quit rates of 6% with nicotine replacement therapy, 6% with e-cigarettes without nicotine and 5% with no support or only behavioural interventions.

“Quitting smoking is hard and a lot of people who smoke will have tried many times to quit smoking and been unsuccessful,” adds co-author Dr Nicola Lindson, University of Oxford.

“For that reason, it is important that there are a number of different options available to help somebody quit, which could encourage them to keep trying. Although nicotine vapes are unlikely to be completely risk free, they are less harmful than smoking and that is the most important comparison to make for people who are still smoking tobacco,” she says.

How toxic is nicotine?

The Cochrane review “found no evidence of increased serious harm from using e-cigarettes to quit”, although longer-term studies are needed. Indeed, another recent review shows that nicotine is far from benign.²

“We wanted to settle a question that has been argued for years: is the harm caused by nicotine related to smoking or is nicotine toxic by itself?” says lead author Professor Thomas Münzel, University Medical Centre Mainz, Germany.

“We now show that nicotine activates receptors on blood vessel cells that switch off the enzyme that keeps vessels relaxed and open. This floods the vessel wall with damaging molecules and sets off a self-amplifying cycle of inflammation and clot formation. The pathway is active regardless of how the nicotine is delivered.”

Nicotine’s harmful cardiovascular effects include activating the sympathetic nervous system, raising blood pressure, increasing heart rate, driving systemic oxidative stress, and promoting vascular inflammation, cardiac remodelling and fibrosis.²

In the endothelium lining blood vessels, nicotine suppresses prostacyclin – a vasodilator and anticoagulant – and releases endothelin-1, a powerful vasoconstrictor. Nicotine also blocks ATP-sensitive potassium channels and disrupts calcium handling in vascular smooth muscle.²

“Nicotine doesn’t only disable the vessel’s protective lining – it directly tightens the muscle around it,” Münzel explains. “These are two separate attack routes converging on the same outcome: a vessel that constricts more, relaxes less and clots more easily.”

Hierarchy of harm

Tobacco and cigarette smoke contain more than 9,000 chemicals. E-cigarettes, heated tobacco and oral nicotine products reduce exposure to toxins produced by combustion. However, they can compromise endothelial function, increase oxidative stress and arterial stiffness, activate the sympathetic nervous system and trigger inflammation.

Many people smoke and vape. A steep, non-linear dose-response relationship links smoking and CVD, so intermittent cigarette smoking may still “confer considerable vascular risk”.²

Münzel and colleagues identified “a consistent hierarchy of vascular harm”. Each product has “a distinct signature of toxicant exposure” that includes not only nicotine, but also aldehydes and volatile organic compounds, particulate matter and metals, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, carbon monoxide and flavourings.²

Toxicity, Münzel and colleagues say, is very high with cigarettes and waterpipes. They consider heated tobacco products and e-cigarettes to have high and moderate toxicity respectively. Snus has mild-to-moderate toxicity, while oral nicotine pouches, lozenges and flavoured nicotine-infused ‘toothpicks’ show mild toxicity.² However, “long-term outcome data for e-cigarettes and newer oral nicotine products [is] not available”.

Nicotine-containing products are rapidly evolving, so the review calls for “a comprehensive … directive that regulates nicotine itself across all delivery platforms”.²

“Nicotine’s cardiovascular toxicity at the molecular level, combined with its well-documented, high dependence-forming potential make the case for a coherent, nicotine-based regulatory framework rather than the current patchwork of product-specific rules,” Münzel concludes.

References

1. Cochrane Database of Systematic Reviews. doi: 10.1002/14651858.CD010216.pub11
2. Nature Reviews Cardiology. doi: 10.1038/s41569-026-01331-6