The Error of Equivalence
About Nicotine Pouches: What Farsalinos’s Review Reveals When Combustion Leaves the Equation.
When a smoker lights a cigarette, the body has no choice; it complies. Within seconds, a cocktail of thousands of compounds moves through the airways and spills into the bloodstream, reaching the lungs, the brain, the heart.
Yes, there are carcinogens. But there are also irritants and toxins that begin sabotaging the organism long before any tumor announces itself: chronic inflammation, vascular dysfunction, emphysema, and acute events.
Some of the names sound almost didactic in their cruelty, as if chemistry, with a professor’s composure, had drafted a pedagogical script for catastrophe. Benzene, associated with hematologic damage, is no stranger: it also appears in gasoline, and when it enters the body through smoke, it travels through the bloodstream to the bone marrow. Acrolein, a fierce respiratory irritant that history has seen deployed in chemical weapons during the First World War, arrives in the lungs with the familiarity of something that knows the way. And NNAL, a metabolite linked to tobacco-specific nitrosamines, lingers as a signature of exposure, a stubborn mark that does not vanish overnight.
Now imagine that same smoker trading fire for a small white pouch tucked between lip and gum: a discreet envelope of nicotine and excipients dissolving in silence. There is no flame, no smoke, no ash in the tray. Thirty minutes later, plasma nicotine rises enough to blunt the craving, like turning down the volume on an internal alarm.
And the rest?
This is where the narrative begins to lose its sharp edges. When combustion exits the scene, the body no longer “signs off” on easy theses. Without tar, without carbon monoxide, without the toxic choreography of burning, some of the most familiar accusations lose their immediate target. What remains—and in what magnitude—demands a different vocabulary: less moralism, more pharmacology; less menacing smoke in the air, more dose in the blood; more molecule, stripped bare and insistent.
Among available biomarkers, benzene appears nearly absent. Acrolein declines sharply: by 78.8 percent in the biomarker 3-HPMA compared with smokers. And NNAL, the most feared trace of tobacco-specific nitrosamines, falls further still: roughly 91 percent lower in exclusive pouch users, with levels similar to those observed in former smokers who use no nicotine product at all. Here is the sentence politics, on its worst days, prefers to avoid: this is not “feeling” or a “hypothesis.” It is a fact.
This is not a promise printed on a package. It is the kind of story biomarkers tell: molecules that record exposure with the coldness of a lab report and, at times, with the quiet eloquence of a lie detector.
That is one of the keys to the review by Greek cardiologist Konstantinos Farsalinos, “Nicotine pouches: an aid in smoking cessation, or a new public health hazard?” (February 2026).
The axis of the argument is neither “trust the industry” nor “trust the panic.” It is a different imperative, less comfortable and more verifiable: observe what the body records when the smoke stops passing through it. At the same time, accept the gray zone, because biomarkers do not replace decades of epidemiology; at best, they light up the dashboard.
In the real world, this matters because smoking still exacts an obscene toll. Tobacco remains a machine of death on an industrial scale: more than eight million deaths each year, with a disproportionate burden that falls on low- and middle-income countries.
Decades of campaigns, laws, restrictions, and prohibitions were designed to squeeze both supply and demand. And yet a vast contingent of people remains who cannot—or do not wish to—stop consuming nicotine. It is in that gap between the ideal (“total abstinence”) and the real (life, with its shortcuts and relapses) that harm reduction enters not as a slogan but as a persistent tension.
The human body is a biochemical registry office: it stamps exposures. Some of those stamps are so specific to cigarette smoke that they approach testimonial evidence: was here, passed through, remained. The most famous bears a name that sounds lifted from science fiction: NNAL, shorthand for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
NNAL is a metabolite linked to tobacco-specific nitrosamines, particularly NNK, and it has a quality that makes it an inconvenient witness: it is slow to leave. Put simply, the body metabolizes NNK and produces NNAL, and it is this end product that keeps “signing in” long after the cigarette exits the stage. Its trace can be detected 6 to 12 weeks after exposure ceases, because its terminal half-life ranges from 10 to 18 days. In street terms, it is not fooled by an “I quit yesterday.” It is the chemical equivalent of the smell of smoke on a coat: you leave the room, but it stays, and gives you away for weeks.
When a smoker switches from cigarettes to a nicotine pouch, that “tobacco-free” product that, in some places, has become a trend and, in others, a moral panic or a regulatory problem, the body enters an involuntary experiment.
And the first results tend to appear where politics has the least reach (or the least patience): in the laboratory.
It is precisely this kind of data, which shows up in the lab before it shows up in statistics, that structures the central question of Dr. Farsalinos’s review, simple and incendiary: are we looking at a cessation and harm-reduction tool, or at a new public-health risk?
Biomarkers do not answer everything. But they address what most unsettles the debate: what does the body register when combustion is no longer in the equation?
The Body Rewritten: What Changes When Smoke Exits the Scene
The classic promise of tobacco control has always carried a certain moral elegance—heroic, even, in its simplicity: “quit.” But human biology rarely cooperates with such elegance. Dependence is a repeated pharmacology—routine, immediate relief, a daily negotiation with discomfort, and daily life. The review makes a clear and useful distinction: nicotine sustains the bond; combustion carries the damage.
The most direct way to see that difference is not to debate “toxins” in the abstract, wholesale sense, but to follow—almost in real time—the shifts inside the body when someone switches from cigarettes to pouches.
A cross-sectional study of exclusive pouch users (Velo) compared biomarkers of exposure—and some markers of “potential harm”—with those of smokers. The figure that unsettles intuition is NNAL: roughly 91 percent lower among pouch users than among smokers, with levels approaching those of former smokers who use no nicotine product at all.
But the “lie detector” does not reside in a single number; it lives in the coherence of the whole. In the same study, markers tied to classic smoke toxins move in concert: the acrolein signal (3-HPMA) drops by 78.8 percent; benzene (S-PMA), by 97.2 percent; and 1,3-butadiene (MHBMA), by 93.5 percent.
These figures do something the public debate rarely tolerates: they pull “harm reduction” out of the territory of slogan and place it on the cold, impersonal ruler of measurement.
But the story does not end with toxins. Among markers of potential harm, carboxyhemoglobin declines by 46 percent in pouch users; white blood cell counts fall by 19 percent; and fractional exhaled nitric oxide—suppressed in smokers because smoke alters the airway epithelium—rises by 107 percent, approaching the levels observed in non-smokers.
Here, uncomfortable honesty is required: this study was conducted by researchers affiliated with British American Tobacco. That does not make biomarkers “false,” nor does it make scientists pamphleteers—laboratories measure molecules, not motives—but it changes how the findings must be interpreted. It demands transparency, independent replication, and vigilance.
When the switch is tested under controlled conditions, the pattern returns, with greater discipline. In a randomized study, smokers who switched to pouches (on!®) for seven days had significantly lower total urinary NNAL (creatinine-adjusted) and 18 of 19 exposure biomarkers than those who continued smoking, with reductions ranging from approximately 42 to 96 percent. In magnitude, the review notes, these declines align with those observed in the short term under complete cessation.
Yes, that trial, too, carries political economy on its back cover: it was conducted by researchers affiliated with Altria. And here the paradox that public conversation often prefers to soften becomes unavoidable: the industry that helped feed the fire now wants to sell the extinguisher. That does not absolve anyone. But neither does it erase the biological fact that the markers repeatedly suggest: when combustion is removed from the equation, exposure to toxicants plummets.
There is a physiological reality that public policy will have to confront, even when moral revulsion would prefer to look away.
A third layer—perhaps the most “real-world” of all—comes from population data.
An analysis of the PATH Study (Wave 7, 2022–2023) finds that exclusive pouch users have high nicotine exposure but sharply reduced levels of minor tobacco alkaloids—anabasine and anatabine—94 percent and 97 percent lower, respectively—and lower lead levels than smokers. In a nationally representative dataset, the practical separation between “nicotine” and “smoke” begins to take statistical form.
If caution remains necessary, it serves to sharpen the question: not “is this good?” but “where, exactly, does combustion still leave its signature?”
If exclusive pouch users show such large declines in the canonical markers of smoke, the debate must abandon the convenience of treating everything as a variation on the same harm.
Where, then, would an “equivalent” harm to cigarettes reside, and through what mechanisms would it operate if smoke no longer passes through the body?
Farsalinos’s review does not sell the fantasy of zero risk. What it argues—with the caution of someone who knows “safe” is an expensive word—is that, along the continuum of toxicological risk, pouches tend to occupy the lowest end and may approach nicotine-replacement therapies. One condition, however, changes everything: the dominant pattern must be substitution, not the opening of a new pathway to initiation.
The Ghost of Combustion
Combustion is the invisible character in this story. The presence that never appears in the frame yet ruins the film. Nicotine explains why the smoker returns; combustion explains why he gets sick.
What biomarkers do, quietly, is separate these characters. COHb falls because carbon monoxide is produced by the act of burning and by drawing that burn into the lungs. NNAL falls because the chain of tobacco-specific nitrosamines is no longer fed by smoke. And markers linked to benzene, acrolein, and butadiene plunge because they belong to the world of fire, not to that of an oral matrix without combustion.
The review also underscores a practical detail: pouches deliver nicotine efficiently, generally more slowly than cigarettes, yet fast enough to compete with cravings. In harm reduction, the goal is almost never to purify behavior; it is to remove the fire from the mechanism, reduce suffering, and divert from greater harm.
Here, the review reaches for a bridge: the Swedish experience with snus as proof of concept. Not because snus and pouches are identical, but because they share what matters for this story: oral use, nicotine absorbed through the mucosa, and the absence of smoke passing through the lungs.
Farsalinos crosses that bridge through a “worst-case” argument: if snus, which still contains tobacco, has not been associated with lung cancer and does not exhibit the respiratory-damage pattern typical of cigarettes, then a derivative product without processed tobacco leaf, with far lower levels of harmful constituents, appears plausibly even less risky.
“Plausible,” here, is a scientific term: it asks not for faith, but for confirmation.
But bridges develop cracks. And it is in those cracks—not in the span itself—that public policy tends to lose its footing.
What We Still Don’t Know
Two nearly symmetrical errors circle this debate. The marketing error is to turn biomarkers into a seal of “safety.” The panic error is to treat the absence of twenty years of epidemiology as if it nullified, by decree, robust evidence of reduced exposure.
“Biomarkers are powerful, but they are surrogates: they measure the pathway of harm, not the final outcome.” Lowering NNAL does not “prove” that cancer rates will decline decades from now. Yet, from a biological standpoint, it is difficult to argue that large, sustained reductions in exposure would not, over time, alter risk, as one toxicologist who requested anonymity told me.
Scientific honesty resides in gray zones. And here, those zones have names. Long-term epidemiology does not yet exist for pouches because the category is new, and the review calls for research and surveillance. Local effects and oral health: reports of irritation and lesions exist; long-term studies and well-designed comparisons remain limited. At the same time, technical refinements are emerging with increasingly strong supportive evidence—such as Stingfree—awaiting less proof than broader acceptance, large-scale replication, and investment. Dose and standardization: labeling, additives and flavors, and maximum nicotine limits remain rough terrain for regulators.
And then there is the herd of moral elephants in the room: addiction, dependence, habit, need, and pleasure.
Biomarkers do not measure autonomy; they measure molecules. A world with less combustion may, at the same time, be one with more people using nicotine, and that unsettles the debate because it shifts the frame from “absolute evil” to the slipperier ground of “relative harm.”
The review attempts to frame that tension as a public health equation: benefit when use reflects substitution and cessation, versus potential harm when uptake shifts to non-smokers—especially young people—and the still-disputed, never conclusively demonstrated hypothesis of a “gateway” effect.
Youth data, for example, is an alarm that should never be silenced. In the United States, the CDC estimated a 1.8 percent current-use rate of nicotine pouches among middle and high school students in 2024, with a meaningful share reporting frequent or daily use.
That does not prove a gateway to cigarettes—it may even point in the opposite direction—but it proves something simpler, perhaps older: nicotine has always found ways to circulate, adapting to the times by changing containers, rituals, and language. What changes now is not the human impulse, but how it is packaged, marketed, and diffused.
At the same time, regulators are signaling how they intend to treat the category. In January 2025, the FDA authorized the marketing of twenty ZYN products through the PMTA pathway, the first such authorization for nicotine pouches, according to the agency.
This enters the global storyline: countries will oscillate between prohibition and permission, taxation and tolerance, nicotine caps and flavor restrictions. And each decision rearranges the “dopamine market”: who enters, who exits, and who migrates between products, in ways biomarkers alone cannot see.
The Lie Detector of the Public Debate
Why do these kinds of findings so rarely make headlines with the force they might? Because nicotine is a political object. It carries the stigma of tobacco and the muscle memory of decades of industrial deception.
In the public imagination, “nicotine” and “cigarette” have become moral synonyms. But the body does not work with synonyms; it works with metabolic pathways, combustion byproducts, nitrosamines, and COHb.
Biomarkers function as lie detectors precisely because they do not participate in cultural theater. They sign no manifestos, neither for harm reduction nor for condemnation. They record. And so far, the record has been stubbornly consistent: when combustion disappears, the markers associated with smoke decline significantly.
At the same time, public distrust is not gratuitous; it has a history. And it has a present: the fear that discreet, palatable, potent products may expand the consumer base along the same track that ultimately leads to disease. This is the point at which science and politics face one another without recognition: one measures molecules; the other attempts to anticipate mass behavior.
Here is where Farsalinos’s review proves more useful to a reporter than to a pamphleteer: it does not resolve the moral dilemma. It shifts the terrain to where the evidence is hardest to assess: exposure. And it suggests that public impact will depend less on “basic chemistry” than on the social architecture of use: full substitution versus dual use; adult smokers versus curious adolescents; clear labeling versus confusion.
The human body is an implacable archivist. It keeps traces of what has passed through it, of what irritated what did not need to be irritated, of what ignited inflammation without necessity.
When a smoker switches from cigarettes to a pouch, that archive does not become a certificate of virtue; it begins to be rewritten in measurable terms, not as moral redemption but as a change in exposure.
The lie detector absolves no one. But neither does it allow combustion to masquerade as opinion.
Farsalinos, K. Nicotine pouches: an aid in smoking cessation, or a new public health hazard?. Intern Emerg Med (2026). https://doi.org/10.1007/s11739-026-04278-1
