Category: Science

‘Doctors Confused About Nicotine’

Photo: agongallud
More than 75 percent of U.S. physicians believe that nicotine directly contributes to cancer and cardiovascular disease, reports Filter, citing a recent study in the International Journal of Environmental Research and Public Health.
The study assesses the impact of wording on perceptions of nicotine use. Two versions of a questionnaire were given to 926 physicians, asking about the “extent to which they agree or disagree that ‘nicotine’ [version one] or ‘nicotine, on its own,’ [version two] directly contributes to birth defects, CVD [cardiovascular disease], cancer, depression and chronic obstructive pulmonary disease (COPD).”
For version one of the questionnaire, 85 percent and 85.2 percent of physicians “strongly agreed” that nicotine directly contributed to cancer and COPD, respectively. For version two, 69.6 percent and 67.3 percent “strongly agreed” with those statements.
The study showed a difference in perceptions between medical specializations as well—pulmonologists were the least likely to hold misperceptions about nicotine, and family medicine physicians were the most likely to hold misperceptions about nicotine.
“Even after accounting for question version, the proportion of surveyed physicians who believe that nicotine directly contributes to these health outcomes is alarmingly high,” the study authors wrote. “It is possible that participants are conflating the addictive effect of nicotine with the comparatively more harmful effects of tobacco use.”
“It is very important for physicians to understand the relative harm between nicotine and the other 7,000 toxins in tobacco smoke,” said Michelle Bover Manderski, lead researcher. “This is especially important as physicians play a key role in recommending and prescribing FDA-approved nicotine-replacement medications.”
August 4, 2021
SRNT Urged to Undo Industry Exclusion

David O’Reilly (Photo: BAT)
BAT has asked the board of directors of the Society for Research on Nicotine and Tobacco (SRNT) to reverse its decision to ban employees of the tobacco industry from attending the society’s annual conference in 2022.
“We share in SRNT’s stated commitments to the open dissemination of rigorous, peer-reviewed nicotine and tobacco science, with the ultimate goal of reducing public health impact of tobacco use,” wrote BAT Director of Scientific Research David O’Reilly in a letter to the SRNT.
“However, your recent exclusion of employees of the tobacco industry and the contributions of tobacco industry scientists to dialogue at the annual meeting is contrary to your code of conduct and guiding principles.”
Exclusion, O’Reilly noted, impedes “the generation and dissemination of new knowledge concerning nicotine and tobacco.” “In an FDA-regulated market, the industry must routinely provide FDA regulators with scientific evidence about its products. As a result, some of the best science in the tobacco and nicotine space is being generated from tobacco companies,” he wrote.
Exclusion also undercuts the SRNT’s commitment to “open science without bias,” “promoting scientific dialogue” and “empowering members to make their own informed decisions,” according to O’Reilly. “The board’s decision contradicts the evidence-based principles that underpin the U.S. policy approach, which prioritizes science, irrespective of the source,” O’Reilly wrote.
“In light of our concerns, we respectfully request that the SRNT board reconsider its decision and reaffirm that ‘SRNT is committed to nicotine and tobacco researchers around the world.’”
August 2, 2021
Scientific Partnerships for Sustainable Change

Photo: BAT
Options for the tobacco industry to demonstrate its responsible approach
By Stephane Colard
The objective to limit or even to ban tobacco is on the health and regulatory agenda. The so-called endgame strategy is an official goal in countries such as New Zealand¹ and Ireland.² More globally, the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) was adopted by the World Health Assembly in 2003 and has been ratified by more than 180 countries to date. This convention is composed of a set of articles to reduce tobacco demand and supply and is seen as an accelerator for sustainable development.³
Even if a total ban seems unrealistic at the moment because politicians know that prohibition leads to criminality, tobacco product manufacturers cannot ignore this objective and its possible consequences on the performance of their tobacco business, which is legal. It appears clearly that such a regulatory agenda will have massive impacts along the whole value chain from the production of the raw material up to sale, and sustainable value creation may well require serious business transformations in the near future.
Article 5.3⁴ of the FCTC recommends to “denormalize and, to the extent possible, regulate activities described as ‘socially responsible’ by the tobacco industry, including but not limited to activities described as ‘corporate social responsibility.’” These elements tend to show that corporate and social responsibility (CSR) initiatives having the sole objective of improving the image of tobacco companies will be combatted and will fail and that the needed tobacco business transformation for ensuring sustainable value creation will not be an easy journey; it will succeed only if CSR initiatives support a genuine ambition and if corresponding impacts are assessed with internationally acknowledged methods.
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There are several options for the tobacco industry to demonstrate its responsible approach: compliance with regulations (mandatory); ISO certification or other acknowledged standard(s) (voluntary); disclosure of relevant information to the public and/or the authorities (mandatory or voluntary); and scientific research and publication in peer-reviewed journals (voluntary). The possibility to link company strategies with the United Nations’ Sustainable Development Goals⁵ is also an opportunity to consider.
The U.N. recognizes that a successful sustainable development agenda requires partnerships between governments, the private sector and civil society. The players of the tobacco and alternative product sectors fully understand that no goal can be achieved alone and that partnerships with multiple stakeholders are necessary to meet sustainable development ambitions. For example, some manufacturers prepare their program for child labor prevention in collaboration with the Eliminating Child Labor in Tobacco-growing Foundation (ECLT) and the International Labor Organization (ILO), and others contribute to WASH⁶ programs led by UNICEF.
Dialogue and co-development of solutions to the issues faced by business partners, such as suppliers and retailers, are also collaborative approaches for building a sustainable future together. The misinterpretation of article 5.3⁷ of the FCTC tends to forbid any contact with the tobacco industry, and the strategy of denormalization and isolation aims to prohibit partnerships. However, how could one improve the population health without encouraging or collaborating with the industry to develop and sell reduced-risk alternative products? How could one help millions of tobacco farmers worldwide to combat poverty and hunger without working with them on diversification? How could one combat criminal organizations making profits by the illicit trade of tobacco products without collaborating with the legal businesses? More pragmatically, how could one align government and industry testing laboratories without collaborative studies?
Science should step away from politics, and there is no good reason for justifying absence of partnerships or reluctance to build them in total transparency. This would simply delay the implementation of positive changes. The U.N. underlines that partnerships shall be built upon principles and values, and this is why it is crucial for the tobacco industry to make the meaning of the word “sustainability” very clear in the context of partnership.
It does not mean building partnerships for a sustainable development of tobacco businesses; it means building long-term partnerships to support transformation enabling the creation of sustainable shared value. It is essential to make a distinction between partnership types, as there are at least four different levels of engagement and shared responsibility: a partnership to elaborate a program that the manufacturers will own and manage autonomously and independently; a partnership to prepare a consensual program that the partners will own and manage together; a partnership to prepare a consensual program that a third party will manage; and a full delegation to a partner for elaborating and managing a program.
There is always a reason to choose one type of partnership rather than another, depending on the level of interaction, shared responsibility or independence expected. Each type of partnership can be justified and understood for some given situations, but the reporting of partnerships in a public integrated report should be associated with a transparent communication of the governance rules. The analysis of the degree of interaction and interdependence between stakeholders and the related risks is an essential step because a key stakeholder involuntarily ignored and isolated (for example, the community) could impair the success of the joint project; ISO Standards 26000 and 44001⁸ provide useful guidance in this area.
Transparency is a way to avoid misinterpretations or even the worst suspicions that can totally undermine the good intentions of the partners. Governance is a way to avoid unintended consequences of partnerships, for example, a conflict of interest. The need for science-based methods for assessing impacts of actions for transformation should open a field for transparent and productive scientific partnerships, contributing to accelerate the U.N. agenda and to achieve a shared vision of a better world. There are principles and values in science that are universal (common to public and private sectors), such as transparency on assumptions and results, honesty and clarity in interpretations or capacity to replicate experiments.
The process of peer-reviewed publication is also a good protection against junk science; the fact remains that several journals have decided not to publish any work from scientists working for, or from independent scientists working with, the tobacco industry⁹, peer-reviewed or not. However, it is unfortunate to observe that too many battles of numbers still highlight a lack of consensual methods among specialists, which extends the time spent on discussions and finally postpones the implementation of actions. An example illustrates this point: In 2018, the WHO published a global environmental footprint¹⁰ relative to cigarette smoking. The document reported a 2.6-ton carbon dioxide equivalent per million cigarette sticks while British American Tobacco and Philip Morris International reported 0.79 ton and 0.6 ton carbon dioxide equivalent per million sticks, respectively. The WHO was unable to understand why the figures were different but assumed a difference in scope and varying assessment methodologies. This point highlights a need for more transparency in scope and consensus in methodologies even if general publicly available protocols already exist.¹¹
An association like Coresta,¹² promoting cooperation, can be the platform that the stakeholders need. It is in a privileged position to initiate new scientific and transparent partnerships and forge a consensus on methodologies for measuring the transformations of tobacco companies, far from political positioning, strategic fragmentation and the isolation of legitimate players.
References:
¹ www.health.govt.nz/our-work/preventative-health-wellness/tobacco-control/smokefreeaotearoa- 2025
² https://health.gov.ie/wp-content/uploads/2014/03/TobaccoFreeIreland.pdf
³ www.who.int/fctc/implementation/publications/who-fctc-undp-wntd-2017.pdf?ua=1
⁴ www.who.int/fctc/guidelines/article_5_3.pdf
⁵ www.un.org/sustainabledevelopment/sustainable-development-goals
⁶ Water, Sanitation and Hygiene
⁷www.who.int/fctc/guidelines/article_5_3.pdf
⁸ ISO 44001 Collaborative business relationship management systems—Requirements and framework
⁹ See www.tobaccoreporter.com/2016/06/bat-criticizes-science-censorship
¹⁰ www.who.int/fctc/publications/WHO-FCTC-Enviroment-Cigarette-smoking.pdf
¹¹ See, for example, the Carbon Disclosure Project www.cdp.net/en and the GHG protocol https://ghgprotocol.org
¹² www.coresta.org
Stephane Colard is secretary general of Coresta.

August 1, 2021
Clearing the Smoke

James Murphy (Photos: RAI)
Reynolds’ James Murphy discusses the challenges and
opportunities for tobacco harm reduction.
By Stefanie Rossel
In September 2020, James Murphy took over as executive vice president of research and development at Reynolds American Inc. (RAI), a subsidiary of British American Tobacco and the second-largest tobacco company in the U.S. Tobacco Reporter caught up with Murphy to discuss the challenges and opportunities he faces in his position.
Tobacco Reporter: Upon assuming your position, you conducted a poll among 2,000 U.S. consumers. What were the main findings, and what do you make of them?
James Murphy: We did a poll of 21-plus adults to examine issues related to tobacco harm reduction [THR] because it is an incredibly important priority for us. The results were consistent with other published research; there is confusion about whether innovative products—such as e-cigarettes—present less risk, and in particular, the role of nicotine as a cause of harm.
A similarly large proportion misunderstand nicotine as a cause of smoking-related diseases. Many adult smokers simply do not know that the toxicants generated from tobacco combustion—rather than nicotine or tobacco itself—is the leading cause of smoking-related health harm. Lack of information creates steep barriers for adult smokers to consider a switch to smoke-free tobacco and nicotine alternatives that are potentially less harmful to their health.
Misunderstandings about innovative alternative products, and nicotine itself, are a hurdle toward shared progress. The good news is that reducing harm from combustible tobacco products was considered an important public health priority by more than two-thirds—70 percent—of the adults we surveyed. Thus, there is strong public recognition of the need for innovative solutions to the harms caused by smoking.
This data underscores our commitment and focus on building productive working relationships with legislators and regulators around the country in pursuit of our common goal: reducing smoking rates, keeping tobacco products away from teenagers and ultimately reducing the harm from smoking in America.
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Amid all restrictions on tobacco industry communications, what can the sector do to change consumers’ misperceptions on these issues and encourage smokers’ movement to less hazardous products?
This is a significant issue, and we are engaging with policymakers and legislators—many of whom share such misunderstandings—and the larger scientific and regulatory community. Misunderstanding of nicotine impairs harm reduction, and it must be addressed. As is well studied and understood, the toxicants from the combustion of tobacco drive smoking-related morbidity and mortality.
Yet behavioral research confirms consumer confusion on this point, and recent population-level data published by the Society for Research on Nicotine and Tobacco (SRNT) highlight that up to 80 percent of U.S. adults incorrectly believe that nicotine is responsible for most of the cancer caused by smoking.
Similarly, misunderstanding vapor and vapor flavors can lead to detrimental policies banning products, flavors and even categories of products, whose removal from market could create the unintended consequence of indirectly pushing adults and minors toward cigarettes. We saw this recently in the Yale School of Public Health study regarding San Francisco’s ban on flavored products, where the author found that it was associated with a significant increase in youth smoking there but not in other jurisdictions without the ban.
Regulatory policy should be based on the relative risks of tobacco products. We are committed advocates for a legislative and regulatory framework that recognizes the continuum of risk and includes risk-proportionate policies on taxation, public use and flavors and other aspects of the product that are important to encouraging adult smokers unwilling to quit to switch from cigarettes. Where regulation is based on scientific evidence and not opinion, public policy will benefit public health and contribute to better understandings of these important products.

RAI’s R&D center
During your recent presentation at the GTNF In Focus event, you hinted at the challenge of assessing the risk profiles of other next-generation products, such as modern oral nicotine, for which no epidemiological data are available yet. Can you elaborate?
The FDA is carefully vetting these products, and I have every confidence that their assessment is science-driven and made against the rigorous statutory standard of “appropriate for the protection of public health.” For newer products, such as THP and modern oral nicotine pouches, like vapor with less than a decade on the market, epidemiological data is still in progress.
In the absence of epidemiology, we use a weight-of-evidence approach comprised of laboratory, clinical and real-world population level studies. In our studies, we include both smokers and smokers who quit smoking as epidemiological gateposts and compare clinical and population outcomes for smokers who switch to the next-generation products (NGPs) against these two smoker statuses.
Consider snus usage in Sweden as a strong illustration of THR in action. Smokers have switched to using snus over several decades, and the country now has the lowest lung cancer rates in the whole of the EU. This epidemiological data is the cornerstone of substantiating the beneficial population health impacts of products like snus in countries like Sweden but also within the USA.
In studies we have conducted and published to date, we have demonstrated that users switching to NGPs have similar biological outcomes to smokers who quit. As quitting has known favorable epidemiological outcomes, we can bridge the switch to NGP to quitting and conclude that both will have similar epidemiological outcomes, which would benefit population health in the long run.
The FDA has announced plans to ban menthol as a characterizing flavor in combustible cigarettes and has suggested that the agency may also reduce the nicotine content in cigarettes. Do you consider such measures as a sufficient incentive for smokers to switch to less harmful alternatives? What else needs to be done?
My concern is that any risk-based product standards on cigarettes will lead to confusion in the marketplace. For example, if a menthol product standard is introduced, smokers might wrongly perceive nonmenthol cigarettes as less risky. We know already that the general population misperceives the risks of nicotine when administered in a combustible product versus a noncombustible product and that there are misperceptions regarding the relative risks of vaping compared to smoking. THR presents a better way of reducing the harms from combustible tobacco use. Today in the U.S., millions of smokers have switched to products like vapor or nicotine pouch products. I have spent my career focused on THR and believe we must enable the introduction of satisfying, reduced harm alternatives that will facilitate the switching of smokers down the risk continuum while at the same time ensuring that adequate safeguards are in place against youth usage.
The FDA has recently spoke of finding this “sweet spot,” and ideally, all stakeholders in the THR debate will collaborate to make that happen.

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What are your current research priorities?
Topline, we’re focused on reducing the health impact of our business based on scientifically substantiated reduced-risk products. These products will improve public health and ensure we have a sustainable future. That means establishing and supporting the weight of scientific evidence that appropriately stewarded noncombustion tobacco and nicotine products manufactured to high-quality standards have a role in THR.
In the U.S., we believe that the FDA will play a key role with their stewardship of the PMTA process to ensure that products which are appropriate for the protection of public health remain on market. This regulatory verification will improve smokers’ confidence in these products and facilitate the mass migration of smokers down the risk continuum. There is a large and growing body of evidence—including from Reynolds’ scientists—to support the reduced-risk potential of these categories.
We take two approaches for assessing the risk profile of noncombustible products: if a product has robust epidemiological data, then that data is used as a basis for risk assessment, but for newer products, in the absence of epidemiology—such as THP, vapor and modern oral products—we use a three-stage assessment of emissions, exposure and risk.
Judging from the results of your poll and from recent FDA moves, such as the proposed ban on menthol and planned maximum, nonaddictive nicotine levels in combustible cigarettes, which direction is THR taking in the U.S.?
We believe our broad portfolio of alternatives to combustible cigarettes can accelerate the population-level health benefits supported by the Family Smoking Prevention and Tobacco Control Act and envisioned by the FDA in its consistent endorsement of a comprehensive nicotine regulatory framework.
Potentially less harmful products must be able to compete effectively with the most harmful products, thus moving smokers down the risk continuum of nicotine products. Vaping bans and high taxes on alternatives that may present less risk than cigarettes will not help us reduce the harm from cigarette smoking.

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What are the gaps in THR science from your point of view?
The biggest gap in THR science is caused by an ongoing boycott by various scientific conferences to publicize and share the latest THR research. The recent news from SRNT banning the tobacco industry from future conferences is particularly disappointing. The largest U.S. scientific conference on nicotine and tobacco research banning industry scientists seems counterintuitive. Moreover, the learning process is not merely what we share, but what we can learn from others. Personally, some of the most valuable professional insights I have received were from other U.S.-based academics commenting on our research during SRNT poster sessions.
Science—particularly science that underpins such important public health goals—deserves to be debated on its merits, particularly when the science on those same products is under scientific review by the FDA.
There is room for more consistent methodologies to ensure the consistent assessment of products as there is sometimes conflicting data published on both sides of the THR debate. There is also a gap in evidence for assessing THR products in that we do not have epidemiological data for newer products like THP, vapor [and] modern oral, which have only been on market for five [years] to ten years. That data gap points to a need for agreed proxies to assess individual risk reduction, such as biomarkers of potential harm and quality-of-life measurements, and other real-world evidence which may play a role.
Stefanie Rossel is Tobacco Reporter’s editorial contributor. An experienced trade journalist, she combines sharp reporting skills with in-depth knowledge of the tobacco and vapor industries. Prior to joining Tobacco Reporter, Stefanie was editor-in-chief at Tobacco Journal International, where she worked for a decade. Fluent in English, German and French, Stefanie covers tobacco news around the world. She is based in Germany.

August 1, 2021
New Technique Reduces Harmful Compounds

Photo: orestligetka
New research by North Carolina State University shows a new technique that can alter plant metabolism, which, when tested in tobacco plants, showed that it could reduce harmful chemical compounds, reports Science Daily.
“A number of techniques can be used to successfully reduce specific chemical compounds, or alkaloids, in plants such as tobacco, but research has shown that some of these techniques can increase other harmful chemical compounds while reducing the target compound,” said De-Yu Xie, professor of plant and microbial biology at North Carolina State University and the corresponding author of a paper describing the research.
“Our technology reduced a number of harmful compounds—including the addictive nicotine, the carcinogenic N-nitrosonornicotine (NNN) and other tobacco-specific nitrosamines (TSNAs)—simultaneously without detrimental effects to the plant.”
The technique uses transcription factors and regulatory elements as molecular tools for new regulation designs. The paper appears in Journal of Advanced Research. Research associate Mingzhu Li is a first author of the paper. Former postdoctoral fellows Xianzhi He and Christophe La Hovary are co-first authors. The research was supported by R.J. Reynolds Tobacco Co.
July 16, 2021
PMI and TissUse to Conduct Joint Research

Photo: vegefox.com
Philip Morris International and TissUse have signed a collaboration agreement to utilize PMI’s InHALES technology in combination with TissUse’s proprietary multi-organ-chip (MOC) platform to enable inhalation exposure of functional human tissues in homeostasis at minute scale in vitro.
The two partners will develop an integrated human aerosol test platform that emulates the entire human respiratory tract in terms of dimension and architecture. PMI has established a platform, InHALES, that matches the architecture and characteristics of the human respiratory tract.
TissUse has established the widely used Humimic MOC platform, which enables functional human tissue response in vitro. A “plug-and-play” interface between the two technologies will allow physiologically relevant exposure to complex aerosols in the background of an in vivo-like organization and breathing performance of the human lungs.
The novel integrated Humimic–InHALES test platform will allow acute and subchronic tests on lung models in combination with miniaturized human liver equivalents, enabling assessment of local effects on the biological barrier of lung epithelia, penetration of substances into blood circulation and eventual systemic effects.
According to PMI, Humimic–InHALES will provide a highly predictive model for assessing respiratory toxicity and systemic human effects of inhaled aerosols and their constituents, such as environmental toxins, smoke particles, airborne pathogens and inhalable medications.
“The agreement meets PMI’s ambitions to extend its competence in aerosol applications to the development of new methods for exploratory research and translational sciences, which will not only help advance the research and development of PMI products but also broadly support biomedical research beyond PMI’s core business,” said Julia Hoeng, global head of discovery at PMI, in a statement.
“This agreement synergizes the complementary ideas, know-how and experience of both companies. We are very much looking forward to enhancing TissUse’s highly innovative product and assay portfolio through this collaboration,” said Reyk Horland, CEO of TissUse.
July 4, 2021
Study Confirms HnB Harm Reduction
Photo: BAT
New research published today in Internal and Emergency Medicine provides the first real-world evidence that people switching from cigarettes to exclusive use of glo, BAT’s flagship tobacco-heating product (THP), can significantly reduce their exposure to certain toxicants and indicators of potential harm related to several smoking-related diseases compared with continuing to smoke.
The results, recorded at six months of a 12-month study, showed that switching completely to glo resulted in statistically significant changes across a range of “biomarkers of exposure” (BoE) and indicators of potential harm, known as “biomarkers of potential harm” (BoPH), compared with continuing to smoke.
For most biomarkers measured, the reductions seen in people using glo were similar to those in participants who stopped smoking completely.
Based on the toxicants measured, glo users showed a:
Significant reduction in a biomarker for lung cancer risk;
Significant reduction in white blood cell count, an inflammatory marker indicative of cardiovascular disease (CVD) risk and other smoking-related diseases;
Improvement in HDL cholesterol associated with reduced risk of CVD;
Improvements in two key indicators of lung health; and
Improvement in a key indicator of oxidative stress, a process implicated in several smoking-related diseases, such as CVD and hypertension.
“These are exciting results as they allow us to understand the potential for reduction of risk that switching completely to glo can deliver,” said David O’Reilly, director of scientific research at BAT, in a statement. “The study shows that smokers switching to glo can reduce their exposure to certain toxicants, which reduces their risk of developing certain smoking-related diseases.
“To have shown a significant reduction in measures of BoPH, some comparable to quitting completely, is very encouraging and provides further scientific substantiation of the harm reduction potential of glo and how it supports our ambition to build ‘A Better Tomorrow’ by reducing the health impact of our business.”
Read more about BAT’s glo trial in Tobacco Reporter’s July 2021 issue.
July 1, 2021
Study: Vaping Better Than NRT for Cessation

Photo: bedya
A new study by Queen Mary University of London, published in Addiction, shows that e-cigarettes are more effective in achieving long-term smoking reduction and cessation than nicotine-replacement therapies (NRT).
The study randomized 135 smokers who had been unable to stop smoking with conventional treatments into two groups—one received an eight-week supply of their choice of NRT and the other received an e-cigarette starter pack with instructions to purchase further e-liquids of their choice of strength and flavor. Products were accompanied by minimal behavioral support.
After six months, 27 percent of those in the e-cigarette group had reduced smoking by at least half compared to 6 percent in the NRT group. Of the participants in the e-cigarette group, 19 percent had stopped smoking altogether versus 3 percent in the NRT group.
“These results have important clinical implications for smokers who have previously been unable to stop smoking using conventional treatments,” said Katie Myers Smith, lead researcher and health psychologist, in Eurasia Review. “E-cigarettes should be recommended to smokers who have previously struggled to quit using other methods, particularly when there is limited behavioral support available.”
“This study shows e-cigarettes can be a very effective tool for people who want to stop smoking, including those who’ve tried to quit before,” said Michelle Mitchell, CEO of Cancer Research U.K., which funded the study. “And research so far shows that vaping is far less harmful than smoking. But e-cigarettes aren’t risk free, and we don’t yet know their long-term effects, so people who have never smoked shouldn’t use them.”
July 1, 2021
Milestone Study

Photos: BAT
A long-term, randomized, controlled trial of BAT’s glo tobacco-heating product lends credibility to the harm reduction potential of the entire category.
By Oliver Porritt
A landmark new clinical study has shown that the health risks of cigarette smoking may be reduced in smokers who completely switch to using tobacco-heating products (THPs).
The research, carried out by BAT, analyzed the changes in a range of biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH). These biomarkers are linked to oxidative stress, cardiovascular and respiratory diseases and cancer, and they were used to compare the potential long-term effects of smoking cigarettes versus THPs and cessation.
Published in the Journal Internal and Emergency Medicine, the results suggest that smokers who switch from cigarettes to exclusive use of BAT’s flagship THP, glo, may benefit from a similar reduction in the risk of developing a number of smoking-related diseases as those who stopped smoking entirely.
To find out more about the study and its implications, Tobacco Reporter caught up with BAT’s director of scientific research, David O’Reilly, whose team led the work.

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Speaking from Liverpool, where he was attending this year’s Global Forum on Nicotine (GFN), O’Reilly said the paper represented a significant moment for both his company and the product category as a whole. “This is a milestone event because this groundbreaking study is the first time the world has seen a successful long-term, randomized, controlled trial of any tobacco-heating product. Until now, no one else has been able to demonstrate over a sustained period that when you switch from cigarette smoking to exclusive use of a THP like glo, the biomarkers of potential harm are reduced to levels similar to that of cessation. This study was long in the planning, and it required careful execution, but when we reviewed the results, we were delighted,” said O’Reilly.
“The biomarkers of exposure go down rapidly, so we weren’t expecting to see any substantial improvements between the positive results we published in an earlier paper, featuring our three-month data, and what we found at six months. But with BoPH, you need to conduct longer studies for beneficial changes to occur. That’s why the six-month data was more important to us than either the three month or even the twelve month time slots. In fact, we aren’t really expecting it to change significantly beyond this point. By the time you get to six months, the cohorts have stabilized in their BoPH. We would anticipate that the 12-month data will provide further validation of this set of results, but the halfway point is therefore absolutely pivotal in this year-long study, and we are very pleased with what we’ve seen,” O’Reilly noted.

While this study focused on our flagship THP, glo, we would be the first to say that this research also importantly supports the category of tobacco-heating products as a whole.
David O’Reilly, director of scientific research, BAT
“Every one of the studies we’ve done on glo, and indeed the work we’ve carried out on our other platforms, is important because they all add to the evidence base for these products, further demonstrating that, while they are not risk-free and are addictive, they are reduced risk if individuals quit smoking and move to them completely. But some types of evidence carry more weight than others, and a long-term, clinical, randomized, controlled study assessing BoPH carries a lot of weight indeed.
“I think this study, along with many others that we and others have published, also adds to the evidence that tobacco harm reduction should be adopted as a tobacco control and public health policy because it’s likely to contribute to the reduction in morbidity and mortality from cigarette smoking.”
He added, “This has been a very successful project, but we have also learned a lot of things that we’ll take into our upcoming studies. Over the next three years, we have around 30 clinical trials planned, and we anticipate that in the future these could be executed in a shorter time period. This is really important because the sooner we obtain this kind of data, the sooner we can engage with external stakeholders and give governments and consumers the confidence that for smokers who would otherwise continue to smoke, switching to these products is a positive thing to do.”

This clinical study was carried out at four sites in the U.K. (Belfast, London, Leeds and Merthyr Tydfil). The participants were healthy smokers or never-smokers of both sexes, aged 23–55, who could go about their day-to-day lives, visiting a clinic just once a month for samples, including blood and urine, to be collected.
The volunteer smokers who did not want to quit were randomly selected to either continue smoking their usual brand of cigarettes or switch to the exclusive use of glo for the duration of the study. A control group of smokers who did want to quit smoking was offered nicotine-replacement therapy (NRT) and/or varenicline provision if requested, together with cessation counselling, while the never-smokers acted as a control. Across these four groups, a total of 339 participants completed the study to six months.
Various BoE and BoPH were assessed at baseline and monthly up to 180 days (six months), and this paper presents the results at the halfway point of the full 12-month study. The use of BoPH, in particular, gives researchers the ability to assess the potential health risks of novel tobacco products in the absence of long-term epidemiological evidence. These newer products have simply not been around long enough to evaluate their impact on clinical outcomes such as cancer, cardiovascular disease and chronic obstructive pulmonary disease. These are conditions that can take decades to develop, but BoPH can provide crucial indicators for these events. Indeed, according to the Institute of Medicine’s 2001 report Clearing the Smoke, BoPH are defined as the “measurement of an effect due to exposure; these include early biological effects, alterations in morphology, structure or function, and clinical symptoms consistent with harm.”
The data from this study show that while the BoE and BoPH remained stable between baseline and six months for the group who continued to smoke, the levels of most BoE reduced significantly for the users of glo, becoming similar to those of the control groups who abstained from cigarette smoking.
More importantly, for those participants who exclusively switched to glo, the following BoPH also saw a favorable change versus continued cigarette smoking: HDL, WBC, FEV1%pred, sICAM, 11-dTx B2, 8-epi-PGF, FeNO and NNAL, and, with the exception of FeNO and NNAL, these changes were comparable to cessation.

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To make sure these results were both reliable and meaningful, the team at BAT told participants about the importance of exclusively using the products they had been assigned, for both the cigarette and glo groups, or abstaining from any nicotine products, other than NRT, in the quitting or never-smoker cohorts. But to ensure the glo users were not smoking cigarettes during the study, the clinics also measured a compound called CEVal. This is a hemoglobin adduct of acrylonitrile (N(2cyanoethyl) valine and, as it is only found in cigarette smoke, O’Reilly says it proved to be a very useful biomarker of compliance.

“In these longer-term studies,” he said, “one of the main challenges has always been knowing whether or not the smokers who have either quit smoking or switched to your test product are compliant because if they’re not, it dilutes the effect of switching in the study and the potential long-term harm reduction associated with switching. To encourage smokers to switch to noncombustible products, you need to have really reliable clinical evidence showing that a complete switch is likely to reduce the risks of developing smoking-related diseases as long as they successfully stay with the product and don’t return to smoking.
“So another breakthrough of this study is the fact we can now use CEVal to ensure compliance among our study participants. Indeed, more people were compliant in this study than we expected, and it is possible that was at least partly down to the fact they were told we would be using CEVal. So going forward, we think CEVal is a really useful tool that we are contributing to the scientific community, and we would recommend others to use it in their future studies to ensure compliance.”

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O’Reilly also said that while this study’s findings were an important step forward, they represented just one aspect of BAT’s stated ambition to build “A Better Tomorrow.” “Our purpose is to reduce the health impact of our business,” he said, “and we are doing that with our product portfolio transformation. So, while this study is part of a broader evidence base for glo, at the same time we’re publishing studies relating to our vaping product, Vuse, and our modern oral product, Velo.
“And while this study focused on our flagship THP, glo, we would be the first to say that this research also importantly supports the category of tobacco-heating products as a whole, and when we’ve completed similar studies on Velo and Vuse, those bodies of evidence will support each of the categories of vaping and modern oral. It’s a really important philosophy at BAT that we build trust in these categories, and that’s not just for our products and brands. With all the current transformation in the tobacco and nicotine landscape, perceptions are changing, but there’s still a long way to go. So I think the fact this study should not just be about one product, but the whole category, is a really important message.”

Oliver Porritt is freelance editorial contributor to Tobacco Reporter. Previously, he worked in the science communications department at BAT.
July 1, 2021
BAT: Modern Oral Comparable to NRT
New research published today indicates that BAT’s modern oral products in the form of tobacco-free nicotine pouches have a toxicant profile that is comparable to nicotine-replacement therapies (NRTs) and much lower than traditional oral snus, a category of products that when used as the sole nicotine product is already established as a reduced-risk product compared with cigarettes.
The study, published in Drug and Chemical Toxicology, analyzed four variants of one of BAT’s modern oral nicotine pouch products Lyft+, three snus products, and two different NRT products in a lozenge and a gum format. Each of these products was tested for a range of known harmful and potentially harmful constituents.
The results showed that the modern oral products had a comparable toxicant profile to NRTs, which are currently considered to be the least risky of all nicotine products. The study also estimated that users of the studied modern oral products are likely to be exposed to far fewer and significantly lower levels of toxicants than those who use snus.
According to BAT, the findings suggest that modern oral products, such as Lyft and Velo, should be placed close to NRTs at the lowest exposure end of the nicotine product toxicant delivery continuum.
“These results add to the growing body of evidence to support the reduced-risk potential of modern oral products compared to continuing to smoke,” said Aaron Williams, head of science and R&D, in a statement.
These results add to the growing body of evidence to support the reduced-risk potential of modern oral products compared to continuing to smoke.
Aaron Williams, head of science and R&D, BAT
“They provide important new evidence to support the role of modern oral products in tobacco harm reduction by demonstrating that they have far fewer and much lower levels of toxicants compared with cigarette smoke and even compared with Swedish-style snus, which is already well established as a reduced-risk product when used as the sole nicotine product.
“This means smokers looking for an alternative nicotine product have another alternative offering greatly reduced exposure to toxicants that comes in an oral format that some may find convenient and easy to use.”
June 16, 2021