A major review published in Nature Reviews Cardiology on 20 August 2026 lays out, in unusual detail, what every nicotine product does to the cardiovascular system — and where nicotine pouches sit on that map.

The answer is nuanced enough to annoy both sides of the harm-reduction debate. Pouches rank lowest in a hierarchy of vascular harm among nicotine products — below cigarettes, waterpipes, heated tobacco and e-cigarettes. But the review's lead finding is categorical: no nicotine-delivery system is safe for the cardiovascular system. Pouches still impair blood-vessel function, raise oxidative stress and arterial stiffness, and activate inflammatory pathways. And the one thing everyone wants to know — what happens over decades of use — simply does not exist in the data yet.

The review was authored by a transatlantic group of cardiologists led by Prof. Thomas Münzel of University Medical Center Mainz, with Prof. Thomas F. Lüscher (Royal Brompton Hospital, Imperial College London, University of Zurich) and Prof. Sanjay Rajagopalan (Case Western Reserve). The authors declare no competing interests.

The hierarchy of harm

The paper's central contribution is a continuum of cardiovascular risk, built from mechanistic, biomarker, preclinical and clinical evidence. From worst to least harmful:

1. Combustion products — cigarettes and waterpipes. Unequivocally the most harmful, driving the global burden of heart attacks, stroke, heart failure and premature cardiovascular death.
2. Heated-tobacco products — lower toxicant exposure than cigarettes, but still deliver nicotine alongside particles and chemicals that injure blood vessels.
3. E-cigarettes (aerosol devices) — remove tobacco combustion, but deliver fine particles, metals, aldehydes and flavouring agents that trigger oxidative stress and inflammation.
4. Oral nicotine products — chewing tobacco and nicotine pouches. Lowest in the hierarchy, but not zero.
5. Abstinence — the only state with no nicotine-driven vascular harm.

Each step down the ladder removes a layer of toxic exposure. Pouches sit at the bottom of the nicotine-product range because they contain no tobacco leaf and produce no combustion or aerosol. But they still deliver nicotine — and nicotine itself is the molecule the review identifies as the central driver of cardiovascular injury.

What nicotine does to blood vessels

The review lays out the mechanism in granular detail. Nicotine activates the sympathetic nervous system, raising heart rate and blood pressure. It promotes oxidative imbalance — an excess of damaging reactive oxygen species over the body's antioxidant defences. It triggers inflammation. And it causes endothelial nitric oxide synthase (eNOS) to "uncouple," meaning the enzyme that normally helps blood vessels dilate instead produces more damaging superoxide.

The net result is endothelial dysfunction — the inner lining of blood vessels stops working properly. The review flags this as an early, integrative warning sign. In human studies, endothelial dysfunction shows up as impaired flow-mediated dilatation (a measure of how well arteries widen), elevated high-sensitivity C-reactive protein and interleukin-6 (markers of inflammation), and increased pulse wave velocity (a measure of arterial stiffness). All three predict a higher risk of cardiovascular events.

A 2022 study the review cites, published in PLoS ONE by Antoniewicz and colleagues, found that chronic snus use in healthy young men altered endothelial function and increased arterial stiffness — a direct demonstration that oral nicotine, even without combustion, affects the vasculature.

Why pouches are not exonerated

The review is careful to say what pouches remove and what they do not. Pouches eliminate the combustion toxicants that make cigarettes the deadliest nicotine product. They avoid the aerosol particles, metals and aldehydes associated with e-cigarettes. On a relative-risk basis, that is a genuine difference.

But the review identifies several reasons pouches cannot be declared safe:

• Nicotine itself is biologically active in the cardiovascular system. The sympathetic activation, oxidative stress, inflammation and endothelial dysfunction the review describes are driven by nicotine — not just by combustion byproducts. Pouches deliver nicotine, often at high doses. A 2024 study by Mallock-Ohnesorg et al., cited in the review, found that tobacco-free nicotine pouches deliver surprisingly high nicotine doses despite their small size.
• Long-term outcome data does not exist. The review states this explicitly: long-term outcome data for e-cigarettes and newer oral nicotine products are not available. Pouches have been widely on the market for less than a decade — far too short for the epidemiological studies that would detect cardiovascular endpoints.
• Mortality signals from related products. The review cites a pooled analysis of eight prospective studies (Byhamre et al., International Journal of Epidemiology, 2021) finding that Swedish snus use is associated with mortality. A separate study (Arefalk et al., Circulation, 2014) found that discontinuing snus after a heart attack reduced mortality risk — suggesting that continued oral nicotine use after a cardiac event is not neutral.
• Flavouring agents and other constituents. The review notes that flavouring agents, metals and other non-nicotine constituents in various nicotine products can independently induce oxidative stress and vascular inflammation. What exactly is in each pouch brand varies, and is not always transparent.

The American Heart Association reached a similar conclusion in its own 2025 policy statement in Circulation. The AHA noted that oral nicotine pouch sales have "increased substantially" but that "no data are available on their cardiovascular or health risks," and that use of some smokeless oral nicotine products is associated with increased mortality in people with ischemic heart or cerebrovascular disease.

What this means in practice

The review does not call for pouches to be banned, nor does it suggest they are equivalent to cigarettes. What it does is refuse to let "lower risk" become "safe." The authors write that eliminating combustion reduces but does not eliminate vascular toxicity — a formulation that applies directly to pouches.

For adults who already smoke, the relative-risk argument is real: moving from cigarettes to pouches removes the combustion toxicants responsible for most cardiovascular death. The review acknowledges this continuum. But for people who do not smoke — particularly young people — the calculation is different. Nicotine is addictive, biologically active in the cardiovascular system, and its long-term effects when delivered through pouches are unknown. The review singles out youth uptake as an "urgent public health challenge" and calls for prevention of initiation, flavour bans, taxation, biomarker surveillance and evidence-based cessation support.

The bottom line from one of cardiology's most authoritative journals is that pouches are not cigarettes — but they are not a free pass either. They sit at the bottom of a hierarchy of harm that still starts above zero, and the decades of data needed to judge their long-term cardiovascular safety simply have not been collected yet.

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SOURCES:

• Münzel T, Kuntic M, Keaney JF Jr, Lurz J, Crea F, Lüscher TF, Rajagopalan S, Daiber A. "Nicotine-containing products and the cardiovascular system: mechanisms and global health implications." Nature Reviews Cardiology, published 20 August 2026. DOI: 10.1038/s41569-026-01331-6. Nature Reviews Cardiology
• Dennison Himmelfarb CR et al. "Impact of Smokeless Oral Nicotine Products on Cardiovascular Disease: Implications for Policy, Prevention, and Treatment: A Policy Statement From the American Heart Association." Circulation 151, e1–e21 (2025). DOI: 10.1161/CIR.0000000000001293. AHA / Circulation
• Antoniewicz L et al. "Chronic snus use in healthy males alters endothelial function and increases arterial stiffness." PLoS ONE 17, e0268746 (2022).
• Byhamre ML et al. "Swedish snus use is associated with mortality: a pooled analysis of eight prospective studies." International Journal of Epidemiology 49, 2041–2050 (2021).
• Arefalk G et al. "Discontinuation of smokeless tobacco and mortality risk after myocardial infarction." Circulation 130, 325–332 (2014).
• Mallock-Ohnesorg N et al. "Small pouches, but high nicotine doses — nicotine delivery and acute effects after use of tobacco-free nicotine pouches." Frontiers in Pharmacology 15, 1392027 (2024).