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Frontiers in Physiology 2020Menthol is a monoterpene alcohol, widely used in several food and healthcare products for its particular odor and flavor. For some decades, menthol has been known to act... (Review)
Review
Menthol is a monoterpene alcohol, widely used in several food and healthcare products for its particular odor and flavor. For some decades, menthol has been known to act on the vasculature directly in the endothelium and vascular smooth muscle, with recent studies showing that it also evokes an indirect vascular response via sensory fibers. The mechanisms underlying menthol's vascular action are complex due to the diversity of cellular targets, to the interplay between signaling pathways and to the variability in terms of response. Menthol can evoke either a perfusion increase or decrease in different vascular territories, an observation that warrants a critical discussion. Menthol vascular actions seem to depend on whether the vascular territory under analysis has been directly provoked with menthol or is located deep/distant to the application site. Menthol increases perfusion of directly provoked skin regions due to a complex interplay of increased nitric oxide (NO), endothelium-derived hyperpolarization factors (EDHFs) and sensory nerve responses. In non-provoked vascular beds menthol decreases perfusion which might be attributed to heat-conservation sympathetically-mediated vasoconstriction, although an increase in tissue evaporative heat loss due the formulation ethanol may also play a role. There is increasing evidence that several of menthol's cellular targets are involved in cardiovascular diseases, such as hypertension. Thus menthol and pharmacologically-similar drugs can play important preventive and therapeutic roles, which merits further investigation.
PubMed: 32317987
DOI: 10.3389/fphys.2020.00298 -
Tobacco Control Nov 2023E-cigarettes with cooling flavours have diversified in ways that complicate tobacco control with the emergence of: (1) Ice-hybrid flavours (eg, 'Raspberry Ice') that... (Review)
Review
E-cigarettes with cooling flavours have diversified in ways that complicate tobacco control with the emergence of: (1) Ice-hybrid flavours (eg, 'Raspberry Ice') that combine cooling and fruity/sweet properties; and (2) Products containing non-menthol synthetic cooling agents (eg, Wilkinson Sword (WS), WS-3, WS-23 (termed 'koolada')). This paper reviews the background, chemistry, toxicology, marketing, user perceptions, use prevalence and policy implications of e-cigarette products with ice-hybrid flavours or non-menthol coolants. Scientific literature search supplemented with industry-generated and user-generated information found: (a) The tobacco industry has developed products containing synthetic coolants since 1974, (b) WS-3 and WS-23 are detected in mass-manufactured e-cigarettes (eg, PuffBar); (c) While safe for limited oral ingestion, inhalational toxicology and health effects from daily synthetic coolant exposure are unknown and merit scientific inquiry and attention from regulatory agencies; (d) Ice-hybrid flavours are marketed with themes incorporating fruitiness and/or coolness (eg, snow-covered raspberries); (e) WS-23/WS-3 concentrates also are sold as do-it-yourself additives, (f) Pharmacology research and user-generated and industry-generated information provide a premise to hypothesise that e-cigarette products with ice flavours or non-menthol cooling agents generate pleasant cooling sensations that mask nicotine's harshness while lacking certain aversive features of menthol-only products, (g) Adolescent and young adult use of e-cigarettes with ice-hybrid or other cooling flavours may be common and cross-sectionally associated with more frequent vaping and nicotine dependence in convenience samples. Evidence gaps in the epidemiology, toxicology, health effects and smoking cessation-promoting potential of using these products exist. E-cigarettes with ice flavours or synthetic coolants merit scientific and regulatory attention.
Topics: Adolescent; Humans; Young Adult; Electronic Nicotine Delivery Systems; Flavoring Agents; Menthol; Tobacco Products; Vaping
PubMed: 35483721
DOI: 10.1136/tobaccocontrol-2021-057073 -
Journal of the National Cancer Institute Jul 2022
Topics: Humans; Menthol; Smokers; Smoking; Tobacco Products; Tobacco Smoking
PubMed: 35445271
DOI: 10.1093/jnci/djac073 -
Tobacco Induced Diseases 2022High income jurisdictions are banning menthol/flavored cigarettes and other tobacco products because they attract young people and create dependence. This study explores...
INTRODUCTION
High income jurisdictions are banning menthol/flavored cigarettes and other tobacco products because they attract young people and create dependence. This study explores the importance of menthol and other flavored tobacco products for tobacco markets in low- and middle-income countries (LMICs), identifies countries where the menthol/flavor share is particularly high or rapidly growing, and identifies strategies tobacco companies are using to develop menthol/flavor markets.
METHODS
Research involved analysis of menthol/flavor market data from 2005 to 2019, a systematic review of academic literature, and a scoping exercise with our advocate contacts in LMICs.
RESULTS
The median menthol/capsule market share of the cigarette market grew significantly (p<0.05) between 2005 and 2019, both in lower and upper middle-income countries [lower: 2.5% (IQR: 0.5-4.0) to 6.5% (IQR: 3.6-15.9); and upper: 4.0% (IQR: 0.8-9.8) to 12.3% (IQR: 3.5-24.3)]. Countries with both high market share and high market share growth were Russia, Guatemala, Peru and Nigeria. No market data were available on low-income countries, but the academic literature suggested high prevalence of menthol use in Zambia. Tobacco industry strategies underpinning growth of menthol/flavored tobacco use in LMICs included in-store marketing and display, colorful packs and non-conventional flavor names.
CONCLUSIONS
Menthol/flavor tobacco products are a growing problem in LMICs. In addition to menthol/flavor bans, we recommend marketing bans, point of sale display bans and standardized packaging.
PubMed: 35498956
DOI: 10.18332/tid/146366 -
Journal of Neuroinflammation Jul 2022No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the...
BACKGROUND
No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke.
METHODS
Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We used Trpm8 gene knockout (Trpm8) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke.
RESULTS
Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 or Trpm8 knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study.
CONCLUSION
Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.
Topics: Animals; Infarction; Ischemic Stroke; Menthol; Mice; Neuroprotective Agents; TRPM Cation Channels
PubMed: 35897101
DOI: 10.1186/s12974-022-02553-4 -
Cancer Epidemiology, Biomarkers &... Oct 2022Smoking is declining, except among current menthol cigarette smokers. This study examines menthol cigarette smoking in the United States.
BACKGROUND
Smoking is declining, except among current menthol cigarette smokers. This study examines menthol cigarette smoking in the United States.
METHODS
Cross-sectional data from 35,279 self-respondent current adult smokers who selected menthol cigarettes as their usual type, across the 2003, 2006-2007, 2010-2011, 2014-2015, and 2018-2019 waves of the nationally-representative Tobacco Use Supplement to the Current Population Survey, were analyzed in SAS/SUDAAN. Menthol cigarette smoking among current smokers was assessed by sex, age, race/ethnicity, employment, geography, and educational attainment. Linear contrasts were used to assess trends.
RESULTS
Overall cigarette smoking (12.6% in 2018-2019 from 17.3% in 2003) and menthol cigarette smoking (4.0% in 2018-2019 from 4.7% in 2003) in the population decreased in 2018-2019 from 2003 (both P < 0.001). Using predicted marginals, adjusted by demographics, menthol smoking among current smokers increased to 33.8% in 2018-2019 from 27.9% in 2003 (P < 0.001). Among current smoking adults, increases in menthol smoking were observed among non-Hispanic Black persons (76.8% in 2018-2019 from 73.0% in 2003), young adults (37.7% in 2018-2019 from 31.7% in 2003), and women (39.6% in 2018-2019 from 32.1% in 2003).
CONCLUSIONS
Smoking and menthol smoking in the population has decreased, yet menthol smoking among current smokers increased from 2003 to 2018-2019. Young adult, female, and non-Hispanic Black current smokers were more likely to use menthol cigarettes than their counterparts; these differences have persisted.
IMPACT
Increased menthol smoking among current smokers, notably young adults, women, and non-Hispanic Black individuals, highlights the need for targeted tobacco control interventions for these health disparity populations.
Topics: Cigarette Smoking; Cross-Sectional Studies; Female; Humans; Menthol; Nicotiana; Tobacco Products; United States; Young Adult
PubMed: 35861654
DOI: 10.1158/1055-9965.EPI-22-0095 -
Tobacco Control Aug 2022The Food and Drug Administration (FDA) has recently banned flavours from pod-style electronic cigarettes (e-cigarettes), except for menthol and tobacco. JUUL customers...
BACKGROUND
The Food and Drug Administration (FDA) has recently banned flavours from pod-style electronic cigarettes (e-cigarettes), except for menthol and tobacco. JUUL customers have quickly discovered that flavoured disposable e-cigarettes from other manufacturers, such as Puff, are readily available. Our goal was to compare flavour chemicals, synthetic coolants and pulegone in mint-flavoured/menthol-flavoured e-cigarettes from JUUL and Puff, evaluate the cytotoxicity of the coolants and perform a cancer risk assessment for pulegone, which is present in both JUUL pods and disposable Puff products.
METHODS
Identification and quantification of chemicals were performed using gas chromatography/mass spectrometry. Cytotoxicity of the coolants was evaluated with BEAS-2B cells using the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer risk of pulegone was calculated using the margin of exposure (MOE).
RESULTS
Menthol was the dominant flavour chemical (>1 mg/mL) in all products from both manufacturers. Minor flavour chemicals (<1 mg/mL) differed in the JUUL and Puff fluids and may produce flavour accents. The concentrations of WS-3 and WS-23 were higher in Puff than in JUUL. WS-23 was cytotoxic in the MTT assay at concentrations 90 times lower than concentrations in Puff fluids. The risk of cancer (MOE<10 000) was greater for mint than for menthol products and greater for Puff than for JUUL.
CONCLUSIONS
Switching from flavoured JUUL to Puff e-cigarettes may expose users to increased harm due to the higher levels of WS-23 and pulegone in Puff products. Cancer risk may be reduced in e-cigarettes by using pure menthol rather than mint oils to produce minty-flavoured e-cigarette products.
Topics: Cyclohexane Monoterpenes; Electronic Nicotine Delivery Systems; Flavoring Agents; Humans; Mentha; Menthol; Tobacco Products
PubMed: 34193607
DOI: 10.1136/tobaccocontrol-2021-056582 -
Journal of Obesity & Metabolic Syndrome Mar 2021Increasing basal energy expenditure via uncoupling protein 1 (UCP1)-dependent non-shivering thermogenesis is an attractive therapeutic strategy for treatment of obesity.... (Review)
Review
Increasing basal energy expenditure via uncoupling protein 1 (UCP1)-dependent non-shivering thermogenesis is an attractive therapeutic strategy for treatment of obesity. Transient receptor potential melastatin 8 (TRPM8) channel activation by cold and cold mimetics induces UCP1 transcription and prevents obesity in animals, but the clinical relevance of this relationship remains incompletely understood. A review of TRPM8 channel agonism for treatment of obesity focusing on menthol was undertaken. Adipocyte TRPM8 activation results in Ca influx and protein kinase A (PKA) activation, which induces mitochondrial elongation, mitochondrial localization to lipid droplets, lipolysis, β-oxidation, and UCP1 expression. Ca-induced mitochondrial reactive oxygen species activate UCP1. In animals, TRPM8 agonism increases basal metabolic rate, non-shivering thermogenesis, oxygen consumption, exercise endurance, and fatty acid oxidation and decreases abdominal fat percentage. Menthol prevents high-fat diet-induced obesity, glucose intolerance, insulin resistance, and liver triacylglycerol accumulation. Hypothalamic TRPM8 activation releases glucagon, which activates PKA and promotes catabolism. TRPM8 polymorphisms are associated with obesity. In humans, oral menthol and other TRPM8 agonists have little effect. However, topical menthol appears to increase core body temperature and metabolic rate. A randomized clinical control trial of topical menthol in obese patients is warranted.
PubMed: 33071240
DOI: 10.7570/jomes20038 -
Nicotine & Tobacco Research : Official... Mar 2023In April 2021, the U.S. Food and Drug Administration announced its intention to issue a product standard banning menthol as a characterizing flavor in cigarettes. Given...
INTRODUCTION
In April 2021, the U.S. Food and Drug Administration announced its intention to issue a product standard banning menthol as a characterizing flavor in cigarettes. Given the potential relevance of national estimates of menthol use to pending legislation, this study estimated the prevalence of menthol use among U.S. adults who smoke cigarettes in 2020 and investigated changes in menthol use from 2008 to 2019 by sociodemographics, mental health, and substance use.
AIMS AND METHODS
Nationally representative annual, cross-sectional data from the National Survey on Drug Use and Health, which included participants ages 18 years and older residing in the United States from 2008 to 2019 and the 2020. Data were analyzed using logistic and linear regression models to estimate trends in menthol use among adults who smoke cigarettes by sociodemographic, mental health and substance use variables (total analytic sample 2008-2019 n = 128 327).
RESULTS
In 2020, 43.4% of adults who smoked cigarettes in the past month used menthol. Menthol use was most common among black adults (80%) and over 50% of those Hispanic, female, young (ages 18-34 years), lesbian/gay, with serious psychological distress, and with cigar use used menthol. Menthol use increased among adults who used cigarettes from 2008 to 2019, overall, and grew more rapidly among adults ages 26-34 years, Hispanic, light cigarette use (1-5 per day), and those who smoked cigars.
CONCLUSIONS
Menthol use has increased among U.S. adults who smoke cigarettes over the past decade. Enacting menthol bans could have a widespread public health impact, especially among younger and minoritized groups.
IMPLICATIONS
Menthol cigarette use increased among individuals who smoke cigarettes from 2008 to 2019 in the United States. In 2020, over 40% of smokers used menthol, and menthol use was considerably higher among adult smokers from racial/ethnic minoritized groups, who were younger and who reported mental health problems. The U.S. Food and Drug Administration seeks to ban menthol as a characterizing flavor in cigarettes; our results suggest that such a ban is likely to have a wide-ranging impact on public health.
Topics: Humans; Female; United States; Adolescent; Young Adult; Adult; Menthol; Cigarette Smoking; Cross-Sectional Studies; Tobacco Products; Racial Groups
PubMed: 36223889
DOI: 10.1093/ntr/ntac214 -
Revista Brasileira de Enfermagem 2022to map the strategies for managing thirst in postoperative adult patients. (Review)
Review
OBJECTIVES
to map the strategies for managing thirst in postoperative adult patients.
METHODS
scoping review was conducted in October 2021 in 19 data sources: 14 databases and 5 platforms to search in the grey literature. It was prepared according to the recommendations of the Joanna Briggs Institute and the checklist of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Nine selected articles were part of the final sample.
RESULTS
there is evidence of strategies to manage postoperative thirst using interventions such as water, ice, mentholated measures, carbohydrate and protein enriched fluid, oral hydrator, flavored gargling, cold gargling, wet gauze, 0.75% citric acid spray, and cold water.
FINAL CONSIDERATIONS
the strategies observed may be reduced to cold and menthol use, salivary stimulants, and early introduction of fluids. The outcomes were positive in all the studies reviewed.
Topics: Adult; Carbohydrates; Citric Acid; Humans; Ice; Menthol; Research Design; Thirst; Water
PubMed: 36228294
DOI: 10.1590/0034-7167-2022-0154