Experts warn vaping alters genes, fruit flavors do most damage

People who vape regularly show altered activity in 3,124 genes across the genome compared with people who do not smoke or vape, according to the study.

While some of the changes (28.8%) relate to how often or how much people vape, scientists say two-thirds (66.6%) is linked to the type of flavors and devices they use.

The findings, published in the journal Frontiers in Oncology, highlight the role of flavor and device type in the biological effects of vaping, and could have implications for future regulations.

Because vapes, or e-cigarettes, are relatively new, their long-term health risks remain unclear.

While chronic diseases take decades to emerge, scientists say changes in expression of disease-related genes can provide early clues about the potential harms of vaping.

Previous research has already shown that vaping — similar to smoking — is linked to changes in gene expression involved in the development of cancer, as well as certain heart and lung diseases.

Study senior author Ahmad Besaratinia said: "One major question still remains: what is driving these changes?

"Is it the act of vaping itself — or is it the intensity and duration of vaping, the characteristics of the products used, or some combination of these?"

Besaratinia and his colleagues at the University of Southern California's Keck School of Medicine compared changes in gene expression among 83 people, including vapers, smokers and non-users.

They found that two-thirds of changes in gene activity could be explained by vape flavor and device type, suggesting the chemical makeup of vaping products and the design and configuration of devices play a major role in their biological effects.

Among vapers, those who used fruit flavors or multiple flavors, as well as advanced refillable devices — sometimes called "mods" — showed more changes in gene expression compared with other groups.

Besaratinia said: "The implication is that each flavor has unique attributes that produce different biological effects.

"This is something regulators should carefully consider when evaluating the health risks or potential benefits of each flavored e-cigarette product."

For the study, researchers recruited 35 vapers, 24 smokers and 24 non-users, including both men and women.

Participants were healthy young adults, and the research team used statistical methods to account for differences in age and sex when they analyzed data on gene expression.

The researchers collected oral cell samples from the inside of each participant's cheek.

Using RNA sequencing, the team examined activity across thousands of genes at the same time, including how changes in one gene may affect other genes or the network of genes.

Compared with people who did not smoke or vape, vapers had altered expression in 3,124 genes.

Vapers also showed more variable patterns of gene activity than smokers.

The analysis showed that different vape flavors produced different changes in gene regulation.

Sweet flavors were linked to changes in 2.9% of affected genes; mint or menthol flavors to changes in 0.9% of affected genes; fruit flavors to changes in 31% of affected genes; and multiple flavors to changes in 64.3% of affected genes.

Higher-generation devices, such as mods, were also associated with the strongest and most consistent changes in gene regulation.

Besaratinia said: "These product differences explained more of the variation in gene regulation than how much or how often people vaped."

The research team also conducted a sophisticated bioinformatics analysis to identify the molecular processes, biological pathways and diseases linked to the gene expression changes they observed.

Among vapers, cancer was linked to the highest number of gene expression changes, followed by endocrine disorders, gastrointestinal diseases and neurological diseases.

The research team say their findings have particular relevance as the Food and Drug Administration (FDA) finalizes official guidance on flavored e-cigarette products.

Besaratinia said: "Regulators have been tasked with verifying that the benefits of using e-cigarettes for adults outweigh the risks posed to youth.

"But we show here that vaping flavored products is associated with disease-related molecular changes, regardless of the user's age."

The research team recommend regulators evaluate products in a more granular way, with greater attention to flavors and device characteristics.

They say mods and other newer devices can deliver higher nicotine levels than earlier-generation vapes.

Many also contain potentially toxic additives designed to make vaping smoother and more appealing.

Besaratinia and his team are now conducting a follow-up study of the chemicals used in vaping liquid to determine which compounds are linked to changes in gene expression.

He added: "Once we identify these chemicals, policymakers could instruct manufacturers to either eliminate these chemicals or reduce their level in e-cigarette products to minimize potential harm."