Determining the health effects of oral nicotine products is difficult for several reasons. These products have only entered the market in the past few years. There have been very few studies of their short-term health effects, and medium and long-terms studies have not been possible. Some of the current research has been performed and/or funded by the tobacco companies that sell these products; an industry with obvious financial conflicts of interest and a long history of deceit.1 Furthermore, a high proportion of people who use oral nicotine products are current or past users of other tobacco products or e-cigarettes. Attributing health effects to oral nicotine compared to these other products is therefore difficult.
Oral nicotine products contain a range of chemicals, including nicotine, flavourants and sweeteners and may include synthetic coolants and small amounts of contaminating toxicants (see Section 18C.4). These chemicals are not inhaled through the lungs as is the case for e-cigarettes and burned tobacco products. Rather, they are held in the mouth, sucked or chewed, to release the chemicals within. Any secreted chemicals may be absorbed into the body across the buccal cavity (the lining of the mouth). These chemicals can reach the blood circulation by diffusing through the buccal tissue into nearby blood vessels. From there, they circulate and may be deposited into various other organs throughout the body. The same chemicals could also be swallowed, potentially affecting the mouth, throat, oesophagus and gastrointestinal tract, as well as being absorbed into the circulation via the gastrointestinal route. Although oral nicotine products could reach and affect a wide variety of organs and systems, there is little research on the fate of chemicals from these products. See Section 18C.4.6 for biomarkers of exposure to chemicals from oral nicotine products.
This section describes the health effects of commercial non-therapeutic oral nicotine products such as nicotine pouches. This does not include products prescribed for nicotine replacement therapy, described in Section 7.16. The health effects of smokeless tobacco products such as snus are described in Section 18A.3.
18C.5.1 Health effects of nicotine use
Nicotine is highly addictive, and symptoms of dependence can develop rapidly following the uptake of smoking. Accidental exposure to nicotine, such as being swallowed or spilt on the skin, can cause acute toxicity. Nicotine exposure from tobacco is known to contribute to adverse health effects during pregnancy, such as preterm birth and stillbirth, and activates multiple biological pathways through which smoking increases the risk of disease.2 Nicotine exposure during adolescence, a time during which the brain undergoes rapid development, may have a long-term negative impact on higher cognitive function and emotional regulation.3, 4 The relationship between smoking and poorer mental health is also likely attributable to chronic nicotine use.5 Use of e-cigarettes containing nicotine is a known cause of seizures, which are considered likely to be caused by nicotine itself.6 Nicotine addiction also maintains the use of tobacco products and e-cigarettes, increasing the risks of known health harms from these products (see Chapter 3 and Section 18.6).
Nicotine pouches and other oral nicotine products deliver levels of nicotine that are consistent with them leading to dependence.7 An non-industry study showed that nicotine absorption from pouches containing 30 mg nicotine was comparable with that from cigarettes.8 The rapid rise in nicotine delivery to the blood from this exposure indicates the addictive potential of the products, and was able to reduce cravings. Industry studies of nicotine in the blood of users also suggest levels of nicotine delivered by pouches similar to that delivered by cigarettes.7
Exploratory research on a group of US adults who use oral nicotine pouches found preliminary evidence of significant dependence. The mean Fagerström Test of Nicotine Dependence-Smokeless Tobacco (FTND-ST) score of participants was 7 out of a total possible of 10 (see Section 6.12 for more information on the FTND tests). However, most of these participants reported current tobacco cigarette and/or e-cigarette use. The study authors stopped short of concluding that oral nicotine products cause dependence, and stated that ‘exploring product-specific dependence will be an essential area for future research’.9
Use of Verve chewable nicotine discs by volunteers resulted in a small increase in nicotine levels in a small, independent study of 13 volunteers.10 In people who smoked who abstained overnight, mean nicotine levels increased from 3.1 to 4.5 ng/ml. The use of nicotine discs by these participants resulted in an increase in mean heart rate, from 69 to 75 beats per minute by 15 minutes after initiation of use.10 Other studies have found inconsistent effects of oral nicotine products on heart rates.8
18C.5.2 Accidental exposure and poisoning
Some oral nicotine products, such as tablets/discs, gummies and gum, resemble non-nicotine equivalents in both their form and their packaging.11 This presentation has the potential to increase the risk of accidental exposure, particularly in children who could mistake the products for food/lollies. A container of 30 Rogue tablets at 4 mg nicotine per tablet has a total of 120 mg of nicotine. Guidelines for clinical practice in Australia state that any child who ingests more than 0.5 mg nicotine per kg of body weight requires medical assessment.12 For a 20 kg child, this would be consumption of 10 mg of nicotine which is only 2.5 tablets at 4 mg/tablet. One case study from the Netherlands describes a nine-year-old boy admitted to hospital suffering from tachycardia (increased heart rate), nausea, dizziness and shivering after consuming one pouch of oral nicotine.13
A study by the German Federal Institute for Risk Assessment reported cases of poisoning from nicotine pouches from poison information centres in Germany.8 In one case, stomach pains were reported by a person who swallowed a pouch containing 20 mg of nicotine. Several other cases were reported involving nausea, vomiting and cold sweats.
18C.5.3 Short-term health effects of nicotine pouch use
There has been very little independent (non-tobacco industry) research on the health effects of oral nicotine products.
An exploratory study of US adults recorded self-reported adverse effects for people who used oral nicotine pouches. 97% of participants reported one or more adverse events. Mouth lesions were reported by 48% or participants, upset stomach by 39%, sore mouth by 37%, sore throat by 21% and nausea by 9% of people.9 These preliminary results indicate that some short-term effects could be caused by oral nicotine pouches, however many of the participants were current or past users of tobacco and/or e-cigarettes. Prospective research in sole-users is necessary to determine the health effects of oral nicotine products.
A study conducted by the German Federal Institute for Risk Assessment reported that all oral pouch users reported irritation of the oral mucosa (lining of mouth) ranging from moderate to severe, whereas this was rare for cigarette users.8
18C.5.4 Comparisons of oral nicotine product use and tobacco use
Numerous studies by the makers of non-therapeutic oral nicotine products have compared these products to cigarettes or other tobacco products. These studies rarely compare users of oral nicotine products to those who abstain from all nicotine/tobacco products, which would enable a better estimate of the health effects of oral nicotine use. There are reports of oral nicotine product use among people that have never used tobacco or nicotine products, particularly adolescents and young adults. Studies that examine health and addiction risks for these users are urgently needed (see Section 18C.6).
Unsurprisingly, industry studies are used to support the claim that oral nicotine product use is less harmful than tobacco use. But these studies predict the risk of harm from biomarkers rather than using direct measures of harm. One study conducted by British American Tobacco of users of Velo nicotine pouches compared biomarkers of potential harm (BOPH) in pouch users compared to people who smoked.14 BOPH measure an effect due to exposure. They include early biological effects, altered functions, clinical symptoms and preclinical changes that are consistent with harm.15 In this study, the levels of four BOPH were lower for nicotine pouch users than for people who smoked. However, for three other BOPH as well as quality of life measures, oral health outcomes and most physiological measures, there was no significant difference between nicotine pouch users and people who smoked. Despite measuring these markers in non-smokers, this study failed to report statistical analysis comparing pouch users and non-smokers.14
Another industry study comparing nicotine levels in users of oral nicotine pouches and cigarettes recorded 16 adverse events associated with pouch use, but did not name any of them.16
References
1. Hendlin YH, Vora M, Elias J, and Ling PM. Financial conflicts of interest and stance on tobacco harm reduction: A systematic review. American Journal of Public Health, 2019; 109(7):e1–e8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31095414
2. US Department of Health and Human Services. The health consequences of smoking - 50 years of progress. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Available from: https://stacks.cdc.gov/view/cdc/21569.
3. England LJ, Bunnell RE, Pechacek TF, Tong VT, and McAfee TA. Nicotine and the developing human: A neglected element in the electronic cigarette debate. American Journal of Preventive Medicine, 2015; 49(2):286–93. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25794473
4. Yuan M, Cross SJ, Loughlin SE, and Leslie FM. Nicotine and the adolescent brain. The Journal of physiology, 2015; 593(16):3397–412. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26018031
5. Taylor GMJ, Lindson N, Farley A, Leinberger-Jabari A, Sawyer K, et al. Smoking cessation for improving mental health. Cochrane Database of Systematic Reviews, 2021; (3). Available from: https://doi.org//10.1002/14651858.CD013522.pub2
6. Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, et al. Electronic cigarettes and health outcomes: Systematic review of global evidence. Report for the Australian Department of Health, 2022, National Centre for Epidemiology and Population Health: Canberra. Available from: https://openresearch-repository.anu.edu.au/bitstream/1885/262914/1/Electronic%20cigarettes%20health%20outcomes%20review_2022_WCAG.pdf.
7. WHO study group on tobacco product regulation. Report on the scientific basis of tobacco product regulation: Ninth report of a WHO study group. WHO technical report series, no. 1047., Licence: CC BY-NC-SA 3.0 IGO.Geneva: World Health Organization, 2023. Available from: https://www.who.int/publications/i/item/9789240079410.
8. German Federal Institute for Risk Assessment (BfR). Health risk assessment of nicotine pouches. 2022. Available from: https://mobil.bfr.bund.de/cm/349/health-risk-assessment-of-nicotine-pouches.pdf.
9. Dowd AN, Thrul J, Czaplicki L, Kennedy RD, Moran MB, et al. A cross-sectional survey on oral nicotine pouches: Characterizing use-motives, topography, dependence levels, and adverse events. Nicotine & Tobacco Research, 2023. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37712111
10. Koszowski B, Viray LC, Stanfill SB, Lisko JG, Rosenberry ZR, et al. Nicotine delivery and pharmacologic response from verve, an oral nicotine delivery product. Pharmacology Biochemistry and Behavior, 2015; 136:1-6. Available from: https://pubmed.ncbi.nlm.nih.gov/26096037/
11. Amirshahi M. What are nicotine gummies? Available from: https://www.poison.org/articles/what-are-nicotine-gummies.
12. The Royal Children's Hospital Melbourne. Nicotine poisoning. Melbourne Available from: https://www.rch.org.au/clinicalguide/guideline_index/Nicotine_Poisoning/.
13. van Oosterhout JPM, van Riel A, van Kruijssen AM, and van Unnik-Treurniet RA. [intoxication of a child by an oral nicotine pouch]. Ned Tijdschr Geneeskd, 2023; 167. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37688459
14. Azzopardi D, Haswell LE, Frosina J, McEwan M, Gale N, et al. Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Biomarkers, 2022:1-12. Available from: https://www.ncbi.nlm.nih.gov/pubmed/36484137
15. Chang CM, Edwards SH, Arab A, Del Valle-Pinero AY, Yang L, et al. Biomarkers of tobacco exposure: Summary of an FDA-sponsored public workshop. Cancer Epidemiology, Biomarkers & Prevention, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28151705
16. McEwan M, Azzopardi D, Gale N, Camacho OM, Hardie G, et al. A randomised study to investigate the nicotine pharmacokinetics of oral nicotine pouches and a combustible cigarette. European Journal of Drug Metabolism and Pharmacokinetics, 2021. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34923602