Nicotine pouches: protocol for a scoping review| Tabaccologia

Introduction

Nicotine pouches are pre-filled pouches similar to snus, but instead of tobacco leaf, they are filled with white nicotine powder. These products are to be placed between the lip and the gum, in the anterior maxillary vestibule [1,2]. They originated in Scandinavia, and their distribution is rapidly expanding to other countries, with major tobacco manufacturers selling their products worldwide. Some noteworthy brands include Lyft by British American Tobacco, Velo by RJ Reynolds Vapor Company, Zyn by Swedish Match, Dryft by Kretek International and Nordic Spirits by Japan Tobacco International [2]. Companies promote nicotine pouches as a harmless, tobacco-free alternative and use terms such as “tobacco-free” or “leaf-free” in product marketing. They come in a variety of flavors and are packaged in fancy cans with colorful logos that have great aesthetic appeal [2,3].

To date, there is a lack of independent research on many aspects of these products, including product ingredients, biomarkers of harm, and evaluation of nicotine delivery. In addition, the relative newness of these products makes it impossible to assess their mid- and long-term effects on human health.

From a tobacco control perspective, research is needed to determine whether nicotine pouches can help smokers switch from cigarettes to a potentially less harmful source of nicotine, or whether these products would instead be used concurrently by smokers, leading to dual use. Most importantly, because nicotine pouches are sold in a variety of fruit flavors and can be used discreetly, these products may appeal to youth and non-smokers. As observed with other products such as electronic cigarettes [4], novel nicotine products have the potential to become widespread among youth and young adults, likely promoting nicotine addiction in this population.

The only available scoping review on nicotine pouches was funded by Imperial Brands PLC [5]. The authors reported financial relationships with many tobacco and nicotine industries, including Imperial Brands PLC, British American Tobacco, JUUL Labs, Shenzhen JWEI Electronics, E-Alternative Solutions, and others. Not so surprisingly, the conclusions of the scoping review are only vaguely critical of nicotine pouches, which “may convey lower health risks compared to smoking”, and the authors conclude that “the population health benefit appears positive”, referring to an “apparent lack of appeal to nicotine non-users and youth”[5]. The fact that this review is the most recent and complete review on the topic reinforces the urgency of an independent scoping review on the topic.

The main aim of our scoping review will be to retrieve all original publications on nicotine pouches in order to assess the current state of available knowledge on the topic, reviewing studies on various topics including chemical characterization, toxicity, perception, regulation and use of nicotine pouches.

Methods

The design of the present scoping review was developed following the Preferred Reporting Items for Systematic review and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist [6], and the results derived from this scoping review will be reported according to this guideline.

Eligibility criteria

We will consider all the original publications providing any knowledge about nicotine pouches. We will include, among others, studies on the toxicity and chemical characterization of nicotine pouches, studies on the perception of nicotine pouches, and studies on their regulation. We will not apply any limitations on study population, thus including studies in vitro, in vivo, and human studies. Also, no specific a-priori exclusion criteria will be set for study design, outcomes of interest, setting and other relevant characteristics. We will only exclude studies not dealing with nicotine pouches, non-peer reviewed papers (e.g., dissertations, conference abstracts and proceedings, editorials) and studies in languages other than English. For any identified reviews on nicotine pouches, we will extract and incorporate additional original articles found within those reviews that were not initially captured by our search strategy.

Information sources and search strategy

We will consider several scientific databases to conduct a systematic literature search, including PubMed/MEDLINE and Embase. The search strategy will be first developed in PubMed using a combination of free terms, and then adapted for use in other databases. The search string will be as comprehensive as possible and could be similar to this one:

((nicotine pouch* [Title/Abstract]) OR (oral nicotine [Title/Abstract]) OR (zyn [Title/Abstract]) OR (lyft [Title/Abstract]))

The literature search will be conducted in June 2024.

Selection of sources of evidence

We will use an EndNote library (i.e., a software for reference management) to combine all the publications found in various databases through the defined search string, and we will delete duplicate records. The retrieved articles will be screened independently by two reviewers to identify publications that potentially meet the inclusion criteria in a two-step screening process. Discrepancies between the two reviewers will be discussed and solved; in case of disagreement, a third reviewer will help to make a final decision. In the first screening, titles and abstracts will be screened. In a second screening, the full text of all the potentially eligible publications will be retrieved and independently assessed for eligibility.

Data charting process and data items

A standardized form in Microsoft (MS) Excel will be used to extract data from each eligible identified article. General information regarding the publication includes: first author, year of publication, study design, country, outcome(s). Specifically, articles will be categorized according to the topic dealt on nicotine pouches, including chemical characterization, toxicity, perception, regulation and use.

Synthesis of results

Once all the relevant studies satisfying eligibility criteria are identified, a descriptive analysis will be performed to show study characteristics and to provide information on the investigated outcomes. Specific analyses will be conducted on the main outcome(s) of interest, once defined. All statistical analyses will be carried out in R and SAS.

Ethics and dissemination

This scoping review does not require approval from an ethics committee since no individual-level data will be collected. This review will be the first comprehensive and fully independent scoping review on nicotine pouches. Previous research has shown that scientific articles supported by the tobacco industry tend to reach conclusions that are more favorable to industry interests, thus supporting novel nicotine-containing products [7-9]. Conducting an independent review will ensure objectivity in the interpretation of the results, which is necessary in order to shed light on the current state of knowledge about nicotine pouches. Our review will identify topics of interest that could be explored in detail in a future systematic review, while highlighting gaps in the scientific evidence on this recently widespread nicotine product and suggesting future original studies on these topics. To disseminate the main findings of this review, we will draft and submit a scientific article to a peer-reviewed journal. The results of our work could have a significant impact on the scientific knowledge on this topic and provide an important input for health policy decisions, particularly for public health organizations such as the WHO and national governmental authorities responsible for public health.

References

1. Jackson MJ, Weke A, Holliday R. Nicotine pouches: a review for the dental team. Br Dent J. 2023; 235:643-6. DOI
2. Robichaud MO, Seidenberg AB, Byron MJ. Tobacco companies introduce ‘tobacco-free’ nicotine pouches. Tob Control. 2020; 29:e145-6. DOI
3. Keogh A. Nicotine pouches. Br Dent J. 2021; 230:61-2. DOI
4. Walley SC, Wilson KM, Winickoff JP, Groner J. A public health crisis: electronic cigarettes, vape, and JUUL. Pediatrics. 2019; 143:e20182741. DOI
5. Grandolfo E, Ogden H, Fearon IM, Malt L, Stevenson M, Weaver S. Tobacco-free nicotine pouches and their potential contribution to tobacco harm reduction: a scoping review. Cureus. 2024; 16:e54228. DOI
6. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018; 169:467-73. DOI
7. Martinez C, Fu M, Galan I, Pérez-Rios M, Martínez-Sánchez JM, López MJ. Conflicts of interest in research on electronic cigarettes. Tob Induc Dis. 2018; 16:28. DOI
8. McDonald A, McCausland K, Thomas L, Daube M, Jancey J. Smoke and mirrors? Conflict of interest declarations in tobacco and e-cigarette-related academic publications. Aust N Z J Public Health. 2023; 47:100055. DOI
9. Pisinger C, Godtfredsen N, Bender AM. A conflict of interest is strongly associated with tobacco industry-favourable results, indicating no harm of e-cigarettes. Prev Med. 2019; 119:124-31. DOI