Cochrane Review Highlights Limited but Promising Evidence for Oral Nicotine Pouches

---

Key Points:

• New Evidence Review: A Cochrane Database of Systematic Reviews analysis evaluated oral nicotine pouches (like Zyn and Velo) as potential tools for smoking cessation and harm reduction. The review examined four short-term randomized controlled trials involving adult smokers.

• Study Findings: Results provide low-certainty evidence that oral nicotine pouches may reduce exposure to toxicants compared to cigarettes but are less effective than e-cigarettes for quitting. No serious adverse events were reported, and side effects were mild (e.g., nausea, mouth irritation).

• Health Impact: Biomarker data showed lower carbon monoxide and nitrosamine levels among pouch users versus smokers, suggesting reduced harm from toxic combustion byproducts.

• Research Gaps: Authors emphasized the need for larger, long-term independent studies to better assess cessation effectiveness and potential health effects.

• Market Growth: Nicotine pouch sales have surged – from 126 million units in 2019 to 808 million in 2022, and up 183.7 percent between 2022 and 2024. The FDA authorized 20 pouch products in January 2025, marking the first-ever marketing approvals for this category.

• Youth Use Remains Low: According to the CDC’s 2024 National Youth Tobacco Survey, only 1.8 percent of middle and high school students used nicotine pouches in the past month, far below youth vaping rates (5.9 percent) and dramatically lower than 2019’s 20 percent vaping peak.

• Continuum of Risk: The FDA recognizes that tobacco products exist on a risk spectrum, with oral products posing far less harm than combustible cigarettes. International evidence from Sweden, where oral nicotine use is widespread, shows Europe’s lowest smoking (6 percent) and lung cancer rates.

• Policy Implications: Oral nicotine pouches represent a promising tobacco harm reduction tool, helping adult smokers reduce toxic exposure without increasing youth use. Policymakers should support research and risk-proportionate regulation to expand access to safer alternatives and accelerate progress toward a smoke-free United States.

---

A new paper published in the Cochrane Database of Systematic Reviews examines the role of oral nicotine pouches in helping adults quit or reduce their use of other tobacco and nicotine products. As a novel harm reduction tool gaining popularity worldwide, nicotine pouches could help shape the American tobacco landscape, and it is imperative that policymakers stay informed on emerging evidence. The review evaluated whether oral nicotine pouches – such as Zyn and Velo – can help adults quit or reduce smoking, whether users experience fewer harms, and whether there are any short- or long-term health risks associated with their use.

The authors searched multiple scientific databases and identified four randomized controlled trials that met inclusion criteria, focusing on participants who used tobacco or nicotine for at least four weeks. The studies assessed several outcomes, including smoking abstinence, serious adverse events, and smoking-related biomarkers. Across the four studies, sample sizes ranged from 30 to 146 participants, all of whom were current smokers; none involved vapers or smokeless tobacco users. Three of the trials were independently funded, while one was supported by a manufacturer of tobacco and oral nicotine products. Each study was short-term – lasting from one to eight weeks – and three were rated as having a high risk of bias, with one judged unclear.

Regarding smoking cessation, one trial comparing oral nicotine use to no support found a slightly higher likelihood of quitting among pouch users (one of eighteen participants) compared to none in the control group, though this represented very low-certainty evidence with results indicating possible benefit, no difference, or potential harm. Another study provided low-certainty evidence that e-cigarettes were more effective than nicotine pouches in helping adults quit. Several studies found that oral nicotine users were exposed to fewer harmful chemicals than smokers. One reported lower levels of tobacco-specific nitrosamines, while another found significantly lower carbon monoxide levels among pouch users compared to those who continued smoking. Across all studies, there were no serious adverse events, and reported side effects were mild, including nausea, shortness of breath, and mouth irritation. Two cases of mild nicotine toxicity occurred among individuals who used both cigarettes and pouches, but these resolved without hospitalization.

Although the review’s conclusions are limited by the small number and short duration of available studies, the findings provide low-certainty evidence that oral nicotine products may help smokers reduce exposure to toxicants and that e-cigarettes may be more effective in supporting cessation. The authors emphasize the urgent need for large, long-term, independent clinical trials to better understand the health impacts of nicotine pouch use.

The review contributes valuable insight into a rapidly expanding segment of the U.S. and global nicotine market. Between August 2019 and March 2022, sales of nicotine pouches increased from 126 million to 808 million units, and the CDC Foundation reports an additional 183.7 percent rise between September 2022 and September 2024 – the largest increase yet recorded. In January 2025, the U.S. Food and Drug Administration issued marketing orders for twenty nicotine pouch products – available in a variety of flavors – marking the first time the agency has authorized this category through the premarket tobacco product application process. The FDA has since launched a pilot program to fast-track additional applications, with newly approved products expected on retail shelves by the end of the year. Even tobacco manufacturers report declining cigarette sales alongside rising oral nicotine sales, reflecting a major shift in consumer behavior.

Despite these increases, youth use of nicotine pouches remains low. According to the CDC’s 2024 National Youth Tobacco Survey, only 1.8 percent of middle and high school students reported past-month use, including 2.4 percent of high schoolers and 1 percent of middle schoolers. By comparison, 5.9 percent of students reported current e-cigarette use, a sharp decline from the 2019 peak when 20 percent of U.S. youth were vaping.

Oral nicotine pouches represent another tool in the broader framework of tobacco harm reduction. Despite ongoing misinformation, not all tobacco and nicotine products carry the same level of risk. The FDA has recognized that tobacco products exist on a continuum of risk, with combustible cigarettes posing the greatest harm and oral products – including pouches, lozenges, and nicotine-replacement therapies – posing the least. Evidence from abroad supports this approach. In Sweden, where snus (a type of oral nicotine product) use is widespread through products like snus, smoking rates are the lowest in Europe – only 6 percent of adults reported daily smoking in 2021 – and rates of lung cancer and other smoking-related diseases are also the lowest on the continent.

Lawmakers should pay close attention to emerging evidence on oral nicotine pouches and other harm reduction products. While U.S. smoking rates have steadily declined, they remain above the World Health Organization’s 5 percent threshold for a smoke-free society. Expanding access to and awareness of safer alternatives for adults who cannot or will not quit smoking could accelerate progress toward that goal and move the United States closer to becoming a smoke-free nation.

Nothing in this analysis is intended to influence the passage of legislation, and it does not necessarily represent the views of Tobacco Harm Reduction 101.