Are flavor-vapes really a safe substitute for nicotine? Illustration: Midjourney
Products that promise the benefits of a familiar habit without the perceived drawbacks have a powerful appeal for consumers. When presented with a well-marketed win-win solution, we tend toward optimism, often assuming an appealing product is harmless until the evidence suggests otherwise.
Nicotine-free vaping is one such example. While researchers have devoted considerable attention to the cardiovascular effects of nicotine-containing e-cigarettes, comparatively little is known about the health consequences of vaping without nicotine. Meanwhile, nicotine-free products have gained popularity, particularly among young users. Why not swap a nicotine hit for a seemingly innocuous flavor fix?
Researchers at USC Viterbi set out to bridge that knowledge gap. In a study published in the Journal of the American Heart Association, they found that nicotine-free e-cigarettes can disrupt the heart’s oxygen supply-demand balance – a measure of whether the heart is receiving enough oxygen to meet its needs.
The study, conducted in animal models rather than human participants at this stage, was carried out by the USC Medical Flow Physics Laboratory (MFPL) in collaboration with researchers at Huntington Medical Research Institutes and the University of California, Irvine. First author Deniz Rafiei, a PhD student at USC Viterbi, worked with MFPL director Niema Pahlevan to investigate how nicotine-free vaping affects the relationship between oxygen delivery and oxygen demand in the heart.
Reframing the experiment
The project grew out of a previous MFPL study comparing conventional cigarettes, nicotine-containing e-cigarettes and nicotine-free vaping. Using standard cardiovascular biomarkers, researchers found little difference between nicotine-free vaping and clean air.
However, Pahlevan suspected those measurements were missing something. “Although we didn’t see any significant differences between the nicotine-free vaping and the air groups with those biomarkers, I noticed some dynamical differences that couldn’t be picked up with the metrics we were using,” he said.
Those observations led the team to investigate the subendocardial viability ratio (SEVR), a measure of the balance between oxygen delivered to the heart and oxygen consumed by it. When oxygen demand consistently exceeds supply, the heart becomes increasingly vulnerable to ischemic injury and cardiovascular dysfunction.
Calculating SEVR required measurements rarely used in vaping research. Researchers needed simultaneous pressure measurements inside the heart and in the aorta throughout the cardiac cycle – a technically demanding procedure made possible through collaboration with investigators at Huntington Medical Research Institutes.
Are men at higher risk?
Sex-specific effects of nicotine-free vaping on myocardial oxygen dynamics
The additional measurements revealed effects that had not appeared in the earlier analysis. When the researchers examined oxygen balance directly, they found markedly different responses in male and female subjects.
Male subjects exposed to nicotine-free vaping experienced a significant decline in oxygen supply and an overall impairment in the balance between oxygen delivery and oxygen demand. Female subjects also exhibited cardiovascular changes, but their systems appeared to compensate by increasing oxygen delivery alongside oxygen demand, preserving the overall balance.
The sex-specific findings were among the study’s most surprising results. “It was very interesting for me that the female body, before menopause, may be able to maintain that balance even while vaping,” Rafiei said. “Men were more exposed to this damage in the oxygen balance.”
The findings do not suggest nicotine-free vaping is safe for women, Rafiei cautioned. “Regardless of whether the female body can compensate for the imbalance, there is still the issue of higher oxygen demand,” she said. “We aren’t yet aware of potential long-term consequences.”
A slow and silent onset
Unlike an acute cardiovascular event, impaired oxygen balance is unlikely to produce immediate symptoms. Instead, the damage may accumulate over time.
According to the researchers, disruptions in oxygen balance can lead to myocardial ischemia and angina, and may contribute to the development or progression of heart failure. “Oxygen balance is one of the key measures of how your heart is doing,” Rafiei said.
“The impacts can develop slowly and symptoms can be hard to spot,” said Pahlevan. “In this case, heart failure develops through a long process which can extend across decades.”
That delayed timeline is part of what makes the findings concerning. Cardiovascular disease rarely emerges during adolescence, but physiological changes associated with later disease can begin much earlier.
Fact over flavor
By identifying a biological pathway through which nicotine-free vaping may influence cardiovascular health, the researchers hope to encourage a more evidence-based conversation about nicotine-free vaping.
Future research will examine older subjects, post-menopausal females and models of existing cardiovascular disease. The team ultimately plans to investigate whether similar patterns emerge in human studies.
“It’s important to know the facts so that we can make informed decisions,” Pahlevan said. “At this stage, this is the most impactful way our results can be translated.”
Published on July 8th, 2026
Last updated on July 8th, 2026