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Nicotine & Tobacco Research : Official... Oct 2020In the 1920s, tobacco companies created a marketing campaign for what would one day be their most profitable series of products: mentholated tobacco cigarettes. Menthol... (Review)
Review
UNLABELLED
In the 1920s, tobacco companies created a marketing campaign for what would one day be their most profitable series of products: mentholated tobacco cigarettes. Menthol provides the smoker with a pleasant mint flavor in addition to a cooling sensation of the mouth, throat, and lungs, giving relief from the painful irritation caused by tobacco smoke. Promising a healthier cigarette using pictures of doctors in white coats and even cartoon penguins, tobacco companies promoted these cigarettes to young, beginner smokers and those with respiratory health concerns. Today, smoking tobacco cigarettes causes one in five US Americans to die prematurely, crowning it as the leading cause of preventable death. In contrast to the dubious health claims by tobacco companies, mentholated cigarettes are in fact more addictive. Smokers of mentholated cigarettes have lower successful quit rates and in some cases are resistant to both behavioral and pharmacological treatment strategies. There is now considerable evidence, especially in the last 5 years, that suggest menthol might influence the addictive potential of nicotine-containing tobacco products via biological mechanisms. First, menthol alters the expression, stoichiometry, and function of nicotinic receptors. Second, menthol's chemosensory properties operate to mask aversive properties of using tobacco products. Third, menthol's chemosensory properties aid in serving as a conditioned cue that can both enhance nicotine intake and drive relapse. Fourth, menthol alters nicotine metabolism, increasing its bioavailability. This review discusses emerging evidence for these mechanisms, with an emphasis on preclinical findings that may shed light on why menthol smokers exhibit greater dependence.
IMPLICATIONS
Mentholated cigarettes have been shown to have greater addictive potential than their nonmentholated counterparts. Evidence is pointing toward multiple mechanisms of action by which menthol may alter tobacco dependence. Understanding menthol's biological functions as it pertains to nicotine dependence will be helpful in crafting novel pharmacotherapies that might better serve menthol smokers. In addition, a better understanding of menthol's pharmacology as it relates to tobacco dependence will be valuable for informing policy decisions on the regulation of mentholated cigarettes.
Topics: Antipruritics; Behavior, Addictive; Humans; Menthol; Smokers; Smoking; Smoking Cessation; United States
PubMed: 31867627
DOI: 10.1093/ntr/ntz239 -
Progres En Urologie : Journal de... Sep 2018Menthol is a natural compound, of which the known effects on human physiology are manifold (a feeling of freshness, decongestant, bowel antispasmodic). Its implication... (Review)
Review
INTRODUCTION
Menthol is a natural compound, of which the known effects on human physiology are manifold (a feeling of freshness, decongestant, bowel antispasmodic). Its implication in vesico-sphincteral physiopathology has been studied since the nineties.
METHOD
Literature review of the previous studies having implied menthol in pelvi-perineal physiology through the articles indexed on the Pubmed database, with keywords menthol, menthol and bladder, menthol and toxicity, and TRPM8. Only articles in English were selected.
RESULTS
Of the 30 articles that were included, most demonstrated the existence of a micturition reflex to menthol and cold, mediated by the C-type nerve to the spine through activation of TRPM8 urothelial receptors. More recent experiments paradoxically showed an inhibitory effect of menthol on detrusor contractility, independently of TRPM8, when muscle tissue is directly exposed to the compound. However, similar effects of targeted cutaneous exposure or urothelial exposure on detrusorian function have also been demonstrated through TRPM8. This receptor also appears to be involved in interstitial cystitis and idiopathic detrusor overactivity. Lastly, the potential toxicity of menthol appears negligible. Most of the referenced studies are related to animal experiments. Of the three studies that implied humans, only one elucidates some therapeutic applications.
CONCLUSION
It seems that menthol and its receptors are involved in vesico-sphincteral physiopathology and could provide therapeutic potential in detrusorian overactivity and interstitial cystitis with reduced toxicity.
Topics: Animals; Antipruritics; Humans; Menthol; Urinary Bladder; Urinary Bladder, Overactive; Urination
PubMed: 30098904
DOI: 10.1016/j.purol.2018.07.002 -
Nicotine & Tobacco Research : Official... Apr 2020Despite the overall decline in the prevalence of cigarette use in the United States, menthol cigarette use among smokers is rising, and evidence shows that it may lead... (Review)
Review
INTRODUCTION
Despite the overall decline in the prevalence of cigarette use in the United States, menthol cigarette use among smokers is rising, and evidence shows that it may lead to more detrimental effects on public health than regular cigarette use. One of the mechanisms by which nicotine sustains tobacco use and dependence is due to its cognitive enhancing properties, and basic science literature suggests that menthol may also enhance nicotine's acute effect on cognition.
AIMS AND METHODS
The purpose of this review is to suggest that the cognitive enhancing effects of menthol may be a potentially important neuropsychological mechanism that has yet to be examined. In this narrative review, we provide an overview of basic science studies examining neurobiological and cognitive effects of menthol and menthol cigarette smoking. We also review studies examining menthol essential oils among humans that indicate menthol alone has acute cognitive enhancing properties. Finally, we present factors influencing the rising prevalence of menthol cigarette use among smokers and the importance of this gap in the literature to improve public health and smoking cessation treatment.
CONCLUSIONS
Despite the compelling evidence for menthol's acute cognitive enhancing and reinforcing effects, this mechanism for sustaining tobacco dependence and cigarette use has yet to be examined and validated among humans. On the basis of the basic science evidence for menthol's neurobiological effects on nicotinic receptors and neurotransmitters, perhaps clarifying menthol's effect on cognitive performance can help to elucidate the complicated literature examining menthol and tobacco dependence.
IMPLICATIONS
Menthol cigarette use has continued to be a topic of debate among researchers and policy makers, because of its implications for understanding menthol's contribution to nicotine dependence and smoking persistence, as well as its continued use as a prevalent flavoring in tobacco and nicotine products in the United States and internationally. As international tobacco regulation policies have begun to target menthol cigarettes, research studies need to examine how flavoring additives, specifically menthol, may acutely influence neurobiological and cognitive functioning as a potential mechanism of sustained smoking behavior to develop more effective treatments.
Topics: Antipruritics; Cognition; Humans; Menthol; Public Health; Reinforcement, Psychology; Smoking; Tobacco Use Cessation; Tobacco Use Disorder
PubMed: 30551213
DOI: 10.1093/ntr/nty264 -
Tobacco Control May 2011To integrate information on cigarette companies' understanding and use of menthol as summarised in published research based on previously internal tobacco industry... (Review)
Review
OBJECTIVE
To integrate information on cigarette companies' understanding and use of menthol as summarised in published research based on previously internal tobacco industry documents with results from large population-based surveys of tobacco use and other independent sources.
DATA SOURCES
Papers published in this supplement of Tobacco Control, together with papers identified using PubMed searches.
RESULTS
Tobacco companies shaped consumer perceptions of menthol cigarettes. Menthol is not just a flavouring agent. Cigarette companies use menthol's ability to mask irritation and provide sensory effects to make menthol cigarettes appeal to youth and health-concerned smokers, in part because menthol makes low-tar cigarettes more palatable. Consistent with targeted marketing, youths, women and African Americans disproportionately smoke menthols. There appear to be complex interactions with addictive effects of nicotine. The ubiquitous addition of menthol by tobacco companies to over 90% of all tobacco products, whether labelled 'menthol' or not, demonstrates that menthol is not simply a flavour or brand. Menthol imparts sensory characteristics to cigarettes and has a complex interaction with nicotine that affects smoking behaviour whether it is perceived or not, or whether cigarettes containing menthol are marketed as 'menthol' or not. Adding menthol increases fine particles in cigarette smoke, which have immediate adverse effects on the risk of heart attack.
CONCLUSION
Information from industry documents, confirmed by independent scientific literature, consistently demonstrates that menthol increases population harm from smoking by increasing initiation and reducing cessation in some groups. Menthol facilitates and increases smoking, which causes disease and death.
Topics: Documentation; Health Knowledge, Attitudes, Practice; Humans; Marketing; Menthol; Public Health; Public Opinion; Smoking; Tobacco Industry
PubMed: 21504926
DOI: 10.1136/tc.2011.043604 -
Toxicology Mechanisms and Methods Oct 2020Menthol, which is a natural cyclic monoterpene alcohol with a minty smell, is one of the main constituents of essential oils that naturally occur in some aromatic... (Review)
Review
Menthol additives to tobacco products. Reasons for withdrawing mentholated cigarettes in European Union on 20th may 2020 according to tobacco products directive (2014/40/EU).
Menthol, which is a natural cyclic monoterpene alcohol with a minty smell, is one of the main constituents of essential oils that naturally occur in some aromatic plants, such as . This natural compound shows many biological properties, such as anesthetic, analgesic, antibacterial and antifungal, immunomodulating, and skin penetration-enhancing. It is added to a variety of goods, such as food, oral-care products, OTC products, cosmetics, and tobacco products. Menthol is not just a simple flavoring agent, especially when it comes to tobacco products. Its ability to 'mask' the negative effects of nicotine and its additional positive sensory effects makes it the most common additive in such products. For the customers, mentholated tobacco products may be mistakenly perceived as less harmful for health, which may increase their consumption. However, as the evidence shows, menthol cigarettes are no safer than conventional cigarettes and may lead to more frequent disease exacerbation during prolonged exposure to smoke from such products. In addition, because of its complex interactions with nicotine, menthol may affect smoking behavior and may increase addiction to nicotine. For those reasons, the European Union banned flavored cigarettes (whose sale size reached more than 3% of the total tobacco product market) by implementing the Tobacco Products Directive (2014/40/EU) on 20th May 2020. While the menthol ban was based on health concerns, the ultimate effect on consumers, regarding potential quitting, is yet to be determined.
Topics: Animals; Commerce; Consumer Product Safety; Europe; European Union; Flavoring Agents; Humans; Menthol; Risk Assessment; Smoking Cessation; Tobacco Products; Tobacco Smoking; Tobacco Use Disorder
PubMed: 32746758
DOI: 10.1080/15376516.2020.1805662 -
Life Sciences Oct 2023Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is...
Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is complex, and still poorly understood. In this work, we used a human osteosarcoma cell line (Saos-2) and analysed the effect of menthol, especially in terms of cellular, subcellular and molecular aspects. We demonstrate that menthol causes increased mitochondrial Ca in a complex manner, which is mainly contributed by intracellular sources, including ER. Menthol also changes the Ca-load of individual mitochondrial particles in different conditions. Menthol increases ER-mito contact points, causes mitochondrial morphological changes, and increases mitochondrial ATP, cardiolipin, mitochondrial ROS and reduces mitochondrial membrane potential (ΔΨm). Menthol also prevents the mitochondrial quality damaged by sub-lethal and lethal doses of CCCP. In addition, menthol lowers the mitochondrial temperature within cell and also serves as a cooling agent for the isolated mitochondria in a cell free system too. Notably, menthol-induced reduction of mitochondrial temperature is observed in diverse types of cells, including neuronal, immune and cancer cells. As the higher mitochondrial temperature is a hallmark of several inflammatory, metabolic, disease and age-related disorders, we propose that menthol can serve as an active anti-aging compound against all these disorders. These findings may have relevance in case of several pharmacological and clinical applications of menthol. SIGNIFICANCE STATEMENT: Menthol is a plant-derived bioactive compound that is widely used for several physiological, behavioural, addictive, and medicinal purposes. It is a well-established "cooling and analgesic agent". However, the exact cellular and sub-cellular responses of menthol is poorly understood. In this work, we have characterized the effects of menthol on mitochondrial metabolism. Menthol regulates mitochondrial Ca, ATP, superoxides, cardiolipin, membrane-potential, and ER-mito contact sites. Moreover, the cooling agent menthol also cools down mitochondria and protects mitochondrial damage by certain toxins. These findings may promote use of menthol as a useful supplementary agent for anti-aging, anti-cancer, anti-inflammatory purposes where higher mitochondrial temperature is prevalent.
Topics: Humans; Menthol; Cardiolipins; Mitochondria; Structure-Activity Relationship; Adenosine Triphosphate; Calcium
PubMed: 37604353
DOI: 10.1016/j.lfs.2023.122032 -
The Yale Journal of Biology and Medicine Sep 2015Mentholated cigarettes gained popularity in the 1950s and were often marketed as "healthy" cigarettes, attributable to their pleasurable mint flavor and cooling... (Review)
Review
Mentholated cigarettes gained popularity in the 1950s and were often marketed as "healthy" cigarettes, attributable to their pleasurable mint flavor and cooling sensation in the mouth, lungs, and throat. While it is clear that nicotine is the primary psychoactive component in tobacco cigarettes, recent work has suggested that menthol may also play a role in exacerbating smoking behavior, despite original health claims. Recent evidence highlights four distinct biological mechanisms that can alter smoking behavior: 1) menthol acts to reduce the initially aversive experiences associated with tobacco smoking; 2) menthol can serve as a highly reinforcing sensory cue when associated with nicotine and promote smoking behavior; 3) menthol's actions on nicotinic acetylcholine receptors may change the reinforcing value of nicotine; and 4) menthol can alter nicotine metabolism, thus increasing nicotine bioavailability. The purpose of this review is to highlight and evaluate potential biological mechanisms by which menthol can alter smoking behavior.
Topics: Animals; Behavior, Addictive; Brain; Drug Synergism; Health Behavior; Humans; Menthol; Models, Biological; Nicotine; Reinforcement, Psychology; Smoking
PubMed: 26339211
DOI: No ID Found -
Phytochemistry Dec 2013Menthol is a cyclic monoterpene alcohol which possesses well-known cooling characteristics and a residual minty smell of the oil remnants from which it was obtained.... (Review)
Review
Menthol is a cyclic monoterpene alcohol which possesses well-known cooling characteristics and a residual minty smell of the oil remnants from which it was obtained. Because of these attributes it is one of the most important flavouring additives besides vanilla and citrus. Due to this reason it is used in a variety of consumer products ranging from confections such as chocolate and chewing gum to oral-care products such as toothpaste as well as in over-the-counter medicinal products for its cooling and biological effects. Its cooling effects are not exclusive to medicinal use. Approximately one quarter of the cigarettes on the market contain menthol and small amounts of menthol are even included in non-mentholated cigarettes. Natural menthol is isolated exclusively from Mentha canadensis, but can also be synthesised on industrial scale through various processes. Although menthol exists in eight stereoisomeric forms, (-)-menthol from the natural source and synthesised menthol with the same structure is the most preferred isomer. The demand for menthol is high and it was previously estimated that the worldwide use of menthol was 30-32,000 metric tonnes per annum. Menthol is not a predominant compound of the essential oils as it can only be found as a constituent of a limited number of aromatic plants. These plants are known to exhibit biological activity in vitro and in vivo such as antibacterial, antifungal, antipruritic, anticancer and analgesic effects, and are also an effective fumigant. In addition, menthol is one of the most effective terpenes used to enhance the dermal penetration of pharmaceuticals. This review summarises the chemical and biological properties of menthol and highlights its cooling effects and toxicity.
Topics: Body Temperature; Humans; Mentha; Menthol; Molecular Structure; Monoterpenes; Oils, Volatile
PubMed: 24054028
DOI: 10.1016/j.phytochem.2013.08.005 -
Mini Reviews in Medicinal Chemistry Jan 2013Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring... (Review)
Review
Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent. Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol's coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.
Topics: Animals; Biological Products; Humans; Menthol; Transient Receptor Potential Channels
PubMed: 23061635
DOI: No ID Found -
Tobacco Control May 2011To determine what the tobacco industry knew about menthol's relation to smoking cessation behaviour. (Review)
Review
OBJECTIVE
To determine what the tobacco industry knew about menthol's relation to smoking cessation behaviour.
METHODS
A snowball sampling design was used to systematically search the Legacy Tobacco Documents Library (LTDL) (http://legacy.library.ucsf.edu) between 15 May to 1 August 2010. Of the approximately 11 million documents available in the LTDL, the iterative searches returned tens of thousands of results. A final collection of 509 documents relevant to 1 or more of the research questions were qualitatively analysed, as follows: (1) perceived sensory and taste rewards of menthol and potential relation to quitting; and (2) motivation to quit among menthol users.
RESULTS
Menthol's cooling and anaesthetic effects mask the short-term negative physiological effects of smoking such as throat pain, burning and cough. This provides superficial physical relief as well as psychological assurance against concerns about the health dangers of smoking that would otherwise motivate smokers to quit. Menthol smokers, particularly women, perceive the minty aroma of menthol cigarettes to be more socially acceptable than non-menthol cigarettes.
DISCUSSION
Consumers believe menthol's sensory effects equate to health protections and that menthol cigarettes are more socially acceptable than non-menthol cigarettes. Menthol in cigarettes may encourage experimenters who find non-mentholated cigarettes too harsh, including young or inexperienced users, to progress to regular smoking rather than quitting, and may lessen the motivation to quit among established menthol smokers. The perception of menthol cigarettes as more socially acceptable lessens the impact of smoking denormalisation on quitting motivation. Menthol makes cigarettes easier and more palatable to smoke and less desirable to quit among established smokers. Fewer smokers quitting contributes to the incidence of tobacco-related diseases.
Topics: Anesthesia; Documentation; Female; Health Behavior; Humans; Menthol; Motivation; Perception; Pleasure; Qualitative Research; Smoking; Smoking Cessation; Social Environment; Taste; Tobacco Industry
PubMed: 21504932
DOI: 10.1136/tc.2010.041947