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Science (New York, N.Y.) Oct 2022The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in...
The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals.
Topics: Animals; Mice; Cold Temperature; Cryoelectron Microscopy; Ligands; Menthol; TRPM Cation Channels; Phosphatidylinositol 4,5-Diphosphate; Thermosensing; Ion Channel Gating; Protein Conformation; Pyrimidinones
PubMed: 36227998
DOI: 10.1126/science.add1268 -
Journal of Addictive Diseases 2022Menthol cigarette use among women who smoke cigarettes during pregnancy is high, but little is known about the factors that contribute to preference for menthol...
BACKGROUND
Menthol cigarette use among women who smoke cigarettes during pregnancy is high, but little is known about the factors that contribute to preference for menthol cigarette use during pregnancy.
OBJECTIVE
This study investigated preferences, perceptions, and intentions to use menthol vs. non-menthol cigarettes in a sample of pregnant women.
METHODS
Pregnant women ( = 124, = 26.2 years, 50% minorities) completed a study investigating the impact of maternal smoking on biobehavioral markers of fetal risk. During the third trimester, participants self-reported preferences (liking, attractiveness, smoothness, interest), perceptions of harm (general, pregnancy-specific), and intentions to use menthol and non-menthol cigarettes. We examined differences in responses based on whether participants endorsed (1) cigarette use during pregnancy (yes/no) and (2) lifetime cigarette use (yes/no).
RESULTS
Sixty-two participants endorsed cigarette smoking during pregnancy (85.5% smoked menthol cigarettes), and 94 participants reported lifetime use. Overall, menthol cigarettes were perceived as more likeable and smoother vs. non-menthol (s < .001) - even among participants who never smoked cigarettes (s < .05). All participants rated both menthol and non-menthol cigarette use as harmful. Compared to participants who did not smoke during pregnancy, participants who smoked during pregnancy rated menthol cigarettes as less harmful for pregnant women ( = .001), while there were no differences between groups in harm perceptions toward non-menthol cigarettes.
CONCLUSIONS
Menthol may increase cigarettes appeal for pregnant women. Implications for regulation of menthol cigarettes are discussed. Future studies may investigate the role of sensory perception, marketing, and health education in influencing these factors.
Topics: Adult; Cigarette Smoking; Female; Humans; Intention; Male; Menthol; Pregnancy; Pregnant Women; Tobacco Products
PubMed: 34751106
DOI: 10.1080/10550887.2021.1981123 -
Nicotine & Tobacco Research : Official... Jan 2021To study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers.
INTRODUCTION
To study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers.
METHODS
We analyzed the three most recent 2005, 2010, and 2015 National Health Interview Survey Cancer Control Supplements. After incorporating propensity score weights adjusting for observed differences between menthol and non-menthol users, we estimated Zero-Inflated Poisson models on hospital nights, emergency department visits, doctor visits, and home visits as a function of menthol use status and other covariates separately for current cigarette smokers and recent quitters (former smokers quitting cigarette smoking ≤ 4 years).
RESULTS
Although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers, they did not differ from current non-menthol smokers in health care utilization. Among recent quitters, those who used to smoke menthol cigarettes had higher odds of having hospital nights than those who used to smoke non-menthol cigarettes. However, we did not find any significant association between menthol use and other health care utilization-emergency department visits, doctor visits, and home visits-among recent quitters. Moreover, compared with non-AA recent quitters, AA recent quitters had higher odds of having home visits, but fewer home visits, if they used to smoke menthol cigarettes.
CONCLUSION
Menthol use was associated with greater hospitalization among recent quitters, and the association between home visits and menthol use differed between AA and non-AA recent quitters.
IMPLICATIONS
This is the first study that used econometric models to study the association between health care utilization and menthol cigarette use and examine whether the association differed between AA and non-AA smokers. Our study found health care utilization did not differ by menthol use status for current smokers, although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers. However, we found menthol use was associated with higher odds of having hospital nights for recent quitters. We also found AA recent quitters had a different association between home visits and menthol use compared with non-AA recent quitters.
Topics: Adolescent; Adult; Black or African American; Aged; Cigarette Smoking; Cross-Sectional Studies; Female; Health Expenditures; Humans; Male; Menthol; Middle Aged; Non-Smokers; Patient Acceptance of Health Care; Smokers; United States; White People; Young Adult
PubMed: 32623471
DOI: 10.1093/ntr/ntaa122 -
BMC Public Health Dec 2017Although menthol was not banned under the Tobacco Control Act, the law made it clear that this did not prevent the Food and Drug Administration from issuing a product... (Review)
Review
BACKGROUND
Although menthol was not banned under the Tobacco Control Act, the law made it clear that this did not prevent the Food and Drug Administration from issuing a product standard to ban menthol to protect public health. The purpose of this review was to update the evidence synthesis regarding the role of menthol in initiation, dependence and cessation.
METHODS
A systematic review of the peer-reviewed literature on menthol cigarettes via a PubMed search through May 9, 2017. The National Cancer Institute's Bibliography of Literature on Menthol and Tobacco and the FDA's 2011 report and 2013 addendum were reviewed for additional publications. Included articles addressing initiation, dependence, and cessation were synthesized based on study design and quality, consistency of evidence across populations and over time, coherence of findings across studies, and plausibility of the findings.
RESULTS
Eighty-two studies on menthol cigarette initiation (n = 46), dependence (n = 14), and cessation (n = 34) were included. Large, representative studies show an association between menthol and youth smoking that is consistent in magnitude and direction. One longitudinal and eight cross-sectional studies demonstrate that menthol smokers report increased nicotine dependence compared to non-menthol smokers. Ten studies support the temporal relationship between menthol and reduced smoking cessation, as they measure cessation success at follow-up.
CONCLUSIONS
The strength and consistency of the associations in these studies support that the removal of menthol from cigarettes is likely to reduce youth smoking initiation, improve smoking cessation outcomes in adult smokers, and in turn, benefit public health.
Topics: Cigarette Smoking; Health Policy; Humans; Menthol; Public Health; Randomized Controlled Trials as Topic; United States
PubMed: 29284458
DOI: 10.1186/s12889-017-4987-z -
Nicotine & Tobacco Research : Official... Feb 2024Tobacco product flavors can increase product appeal, adolescent initiation and experimentation, and difficulty quitting. Flavored tobacco products are not restricted in...
INTRODUCTION
Tobacco product flavors can increase product appeal, adolescent initiation and experimentation, and difficulty quitting. Flavored tobacco products are not restricted in Vietnam or the Philippines despite the high smoking prevalence among those 15 years of age and older (24% and 23%, respectively). There are no published reports to our knowledge on the levels of flavor chemicals in the cigarettes sold in these two countries.
METHODS
Cigarettes were purchased in Vietnam (32 brand variants) and the Philippines (19 brand variants) during 2020. Chemical analyses gave the mg/filter, mg/rod, and mg/stick (= mg/(filter + rod)) values for 180 individual flavor chemicals. Values were calculated for menthol, clove-related compounds, and "other flavor chemicals" (OFCs).
RESULTS
Five flavor groupings were found among the brand variants purchased in Vietnam: menthol + OFCs (n = 15), OFCs only (n = 8), nonflavored (n = 7), menthol + OFCs with a clove flavorant (n = 1) and menthol only (n = 1). Three flavor groupings were found among the brand variants purchased in the Philippines: menthol + OFCs (n = 10), nonflavored (n = 5), and menthol only (n = 4).
CONCLUSIONS
A range of flavored cigarette products are being offered by tobacco companies in Vietnam and the Philippines, presumably to maximize cigarette sales. Regulation of flavor chemicals should be considered in these two countries.
IMPLICATIONS
Article 9 of the WHO Framework Convention on Tobacco Control (FCTC), ratified by both Vietnam and the Philippines, states that "there is no justification for permitting the use of ingredients, such as flavoring agents, which help make tobacco products attractive." Flavors increase product appeal, adolescent initiation and experimentation, and difficulty quitting. These analyses found that cigarettes purchased in Vietnam and the Philippines contained menthol and other flavor chemicals. Tobacco companies are offering multiple flavor chemical profiles and nominally nonflavored versions in these countries; regulation of flavor chemicals should be considered in these two countries.
Topics: Adolescent; Humans; Menthol; Philippines; Vietnam; Flavoring Agents; Electronic Nicotine Delivery Systems; Tobacco Products; Brain; Cleft Lip; Cleft Palate
PubMed: 37578845
DOI: 10.1093/ntr/ntad146 -
Respiratory Research Apr 2023Flavored electronic cigarettes (ECs) present a serious health challenge globally. Currently, it is unknown whether the addition of highly popular menthol flavoring to...
Flavored electronic cigarettes (ECs) present a serious health challenge globally. Currently, it is unknown whether the addition of highly popular menthol flavoring to e-liquid is associated with changes in the number of aerosolized particles generated or altered lung function. Here, we first performed preclinical studies using our novel robotic platform Human Vaping Mimetic Real-Time Particle Analyzer (HUMITIPAA). HUMITIPAA generates fresh aerosols for any desired EC in a very controlled and user-definable manner and utilizes an optical sensing system to quantitate and analyze sub-micron and microparticles from every puff over the course of vaping session in real-time while emulating clinically relevant breathing mechanics and vaping topography. We discovered that addition of menthol flavoring to freshly prepared e-liquid base propylene glycol-vegetable glycerin leads to enhanced particle counts in all tested size fractions, similar to the effect of adding vitamin E acetate to e-liquid we previously reported. Similarly, we found that menthol vs. non-menthol (tobacco) flavored pods from commercially available ECs leads to generation of significantly higher quantities of 1-10 µm particles upon inhalation. We then retrospectively analyzed data from the COPDGene study and identified an association between the use of menthol flavored ECs and reduced FEV1% predicted and FEV1/FVC independent of age, gender, race, pack-years of smoking, and use of nicotine or cannabis-containing vaping products. Our results reveal an association between enhanced inhaled particle due to menthol addition to ECs and worse lung function indices. Detailed causal relation remains to be demonstrated in future large-scale prospective clinical studies. Importantly, here we demonstrate utility of the HUMITIPAA as a predictive enabling technology to identify inhalation toxicological potential of emerging ECs as the chemical formulation of e-liquid gets modified.
Topics: Humans; Electronic Nicotine Delivery Systems; Smokers; Menthol; Prospective Studies; Retrospective Studies; Tobacco Products; Lung
PubMed: 37038183
DOI: 10.1186/s12931-023-02410-9 -
Tobacco Control May 2011To determine what the tobacco industry knew about the potential effects of menthol on smoking topography-how a person smokes a cigarette. (Review)
Review
OBJECTIVE
To determine what the tobacco industry knew about the potential effects of menthol on smoking topography-how a person smokes a cigarette.
METHODS
A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) between 1 June 2010 and 9 August 2010. We qualitatively analysed a final collection of 252 documents related to menthol and smoking topography.
RESULTS
The tobacco industry knew that menthol has cooling, anaesthetic and analgesic properties that moderate the harshness and irritation of tobacco. Owing to its physiological effects, menthol contributes to the sensory qualities of the smoke and affects smoking topography and cigarette preference.
CONCLUSION
Our review of industry studies suggests that the amount of menthol in a cigarette is associated with how the cigarette is smoked and how satisfying it is to the smoker. If menthol in cigarettes was banned, as the US Food and Drug Administration (FDA) is currently considering, new/experimental smokers might choose not to smoke rather than experience the harshness of tobacco smoke and the irritating qualities of nicotine. Similarly, established menthol smokers might choose to quit if faced with an unpleasant smoking alternative.
Topics: Consumer Behavior; Documentation; Habits; Humans; Menthol; Pleasure; Smoke; Smoking; Nicotiana; Tobacco Industry
PubMed: 21504930
DOI: 10.1136/tc.2010.041988 -
Pain Feb 2021
Topics: Ankyrins; Humans; Menthol; Neurogenic Inflammation; Nociception; Pain; Receptors, Nerve Growth Factor
PubMed: 32826762
DOI: 10.1097/j.pain.0000000000002044 -
Toxicological Sciences : An Official... May 2023Menthol and tobacco flavors are available for almost all tobacco products, including electronic cigarettes (e-cigs). These flavors are a mixture of chemicals with...
Menthol and tobacco flavors are available for almost all tobacco products, including electronic cigarettes (e-cigs). These flavors are a mixture of chemicals with overlapping constituents. There are no comparative toxicity studies of these flavors produced by different manufacturers. We hypothesized that acute exposure to menthol and tobacco-flavored e-cig aerosols induces inflammatory, genotoxicity, and metabolic responses in mouse lungs. We compared two brands, A and B, of e-cig flavors (PG/VG, menthol, and tobacco) with and without nicotine for their inflammatory response, genotoxic markers, and altered genes and proteins in the context of metabolism by exposing mouse strains, C57BL/6J (Th1-mediated) and BALB/cJ (Th2-mediated). Brand A nicotine-free menthol exposure caused increased neutrophils and differential T-lymphocyte influx in bronchoalveolar lavage fluid and induced significant immunosuppression, while brand A tobacco with nicotine elicited an allergic inflammatory response with increased Eotaxin, IL-6, and RANTES levels. Brand B elicited a similar inflammatory response in menthol flavor exposure. Upon e-cig exposure, genotoxicity markers significantly increased in lung tissue. These inflammatory and genotoxicity responses were associated with altered NLRP3 inflammasome and TRPA1 induction by menthol flavor. Nicotine decreased surfactant protein D and increased PAI-1 by menthol and tobacco flavors, respectively. Integration of inflammatory and metabolic pathway gene expression analysis showed immunometabolic regulation in T cells via PI3K/Akt/p70S6k-mTOR axis associated with suppressed immunity/allergic immune response. Overall, this study showed the comparative toxicity of flavored e-cig aerosols, unraveling potential signaling pathways of nicotine and flavor-mediated pulmonary toxicological responses, and emphasized the need for standardized toxicity testing for appropriate premarket authorization of e-cigarette products.
Topics: Animals; Mice; Electronic Nicotine Delivery Systems; Menthol; Phosphatidylinositol 3-Kinases; Mice, Inbred C57BL; Nicotine; Lung; Aerosols; Flavoring Agents; Tobacco Products
PubMed: 37052522
DOI: 10.1093/toxsci/kfad033 -
European Review For Medical and... Dec 2022The aim of this paper is to review whether products containing menthol exacerbate allergic rhinitis. A literature survey was performed on PubMed, Google and Google... (Review)
Review
The aim of this paper is to review whether products containing menthol exacerbate allergic rhinitis. A literature survey was performed on PubMed, Google and Google Scholar concerning allergic rhinitis (AR). Allergic rhinitis is an inflammatory condition of the nasal mucosa characterized by wheeze, congestion, nasal pruritus and discharge, or any combination thereof. Menthol is a naturally occurring phytochemical, with the formula C10H20O. The L-isomeric form creates the typical odor of peppermints and causes a sensation of coolness when applied to the skin or mucosae. Inhaling menthol vapor is known to affect the respiratory system in a number of different ways. The cooling agent, menthol, is also recognized as a trigger for asthma, AR and urticaria. The menthol molecule stimulates the TRPM8 receptor and may stimulate histamine release in a dose-dependent manner from RBL-2H3 cell cultures. The addition of menthol to products produces symptomatic relief in some patients by providing an impression of freer nasal air flow. It does this by stimulating cold receptors on branches of the fifth cranial nerve. Menthol is capable of provoking allergic hypersensitivity reactions and disorders, including asthma, AR and urticaria. It may also trigger an anaphylactic response. The use of menthol-containing products is best avoided in cases where an allergic disorder exists.
Topics: Humans; Menthol; Rhinitis, Allergic; Nasal Mucosa; Asthma; Urticaria
PubMed: 36524912
DOI: 10.26355/eurrev_202212_30484