The menthol trap in tobacco/nicotine smoke| Tabaccologia

Article

According to data from the World Health Organization (WHO), there are 1.3 billion smokers in the world, 8.2 million / year [1] of which die from causes related to active and passive tobacco smoking. In Italy, for the same causes, there are about 90,000 deaths per year [2].

The tobacco industry has been working for a long time to make its products increasingly attractive in order to increase, or at least maintain, the number of consumers.

In the 1960s, Philip Morris International Inc. (PMI) launched cigarettes with nicotine added to ammonia [3] on the market, in order to make it more easily absorbable and therefore more capable of inducing chemical addiction to tobacco.

This artifice was discovered and eliminated following the revelations of Jeff Wigand, an insider of Brown & Willianson, which led to a trial where such data were evidenced and authenticated through objective documentation [4, 5].

In the same years, the “big maneuvers” to recruit new customers among the younger population groups of medium/low-income countries and, in particular, among female consumers, had also begun. Tobacco products have been modified in their organoleptic properties with the use of flavourings and additives that have a positive impact especially on consumers’ taste and smell. Among them, menthol has played a leading role for decades and various characteristics regarding its role in triggering and maintaining tobacco addiction, have been studied.

Menthol is a chiral alcohol which, at room temperature, appears as a white solid with a characteristic odour. It is a compound with irritating, refreshing and analgesic properties, extracted from the essential oil of peppermint. It is present in 90% of cigarettes, albeit in different quantities: 0.03% of the weight in tobacco / cigarette in non-mentholated ones, up to 1% in those where it is perceptible, that is, mentholated ones. The sugars present in the wrapper of the cigarette, mixed with menthol, cause an increase in the production of acetaldehyde which is an agent that enhances the additive capacities of nicotine.

As their reinforcement actions on tobacco addiction are becoming increasingly evident, the European Union (EU) issued a specific directive in 2014 under which, starting from 2016, all additives should have been eliminated in tobacco products, with the excepted menthol, for which the producers obtained an extension until May 20, 2020 [6]. But “made the law found the deception”. In fact, this provision is now circumvented with the placing on the market of menthol filters and some types of cigarettes have a small capsule containing menthol in the filter, to be crushed at the desired time to obtain a more pleasant taste and smell from the aspirated cigarette smoke, and have a fragrant and fresh breath at the end of the consumption [7].

Several studies have been conducted in recent years to try to substantiate with the impartiality of scientific data what was already hypothesised, namely that menthol affects, through precise mechanisms of direct or indirect actions, on various parameters concerning public health, based on the role played in addiction to tobacco and alternative products to cigarettes.

The action of menthol in smokers essentially regards the respiratory system, the central nervous system and the hepatic metabolism of nicotine.

Menthol performs multiple actions mediated by transient receptor potential melastatin 8 (TRPM8), which is an almost ubiquitous receptor along the airways [8]. In particular, it is localized on the nerve endings of the trigeminal branches that innervate the nose, mouth (connected to taste and smell) [9] and the upper airways, but also on those of the lower airways. It activates spontaneously when the temperature drops below 26°C and, through a temperature-dependent flow of Ca ++ and K + ions at the level of the non-nociceptive endings, it transmits the sensation of cold. The mediator at the level of the central nervous system (CNS) is glutamate, the release of which is determined by the trans-membrane flux of Ca ++ ions. By acting in this way, menthol perfumes the breath and gives a sense of freshness that leads the smoker to breathe with a forced vital capacity. In addition, it acts on taste and smell by positively modifying the taste of tobacco smoke, suppresses the cough reflex and masks the irritating action of nicotine and other components of tobacco smoke, making it more palatable and inhalable and favouring, especially in beginners, the trigger of addiction. It also exerts an action on the bronchial epithelium, inducing the production of mucin and interleukins-13, 25 and 33, increases the expression of the anti-apoptotic factor Bcl-2, inhibits the metabolism of 4- (methylnitrosamino) -1- (3-pyridyl) -1-butanol (NNAL), tobacco carcinogen [10]; induces, through a mediated TRPM8 pathway, the production of pro-inflammatory interleukins that determine a greater inflammatory response of the bronchial epithelium (which is added to the production of oxygen free radicals, induced by other components of tobacco smoke) ; it worsens broncho-constriction in Chronic Obstructive Pulmonary Disease (COPD) smokers [11-13]. Finally, the menthol contained in the vaporisation liquids of electronic cigarettes and in heated tobacco products acts with exactly the same mechanisms, predisposing to respiratory diseases even with the use of such alternative devices to tobacco [14].

Menthol inhibits cytochrome CYP2A6 in the liver, which provides for the metabolism of nicotine. The area under the curve (AUC) of nicotine is therefore increased and its pharmacokinetics altered in the sense of greater persistence in the blood, slower disposal and more prolonged bioavailability, which on the one hand leads to less recourse to cigarettes, but on the other hand it enhances the additogenic effect of nicotine itself. In addition, menthol enhances the hypothermic and anti-nociceptive action of nicotine and significantly increases the signs of withdrawal (somatic signs, hyperalgesia and anxious behaviours), making it easier for those who try to free themselves from it [15].

Menthol alters the expression, function and stoichiometry of nicotinergic receptors, favouring the action of nicotine on them (in particular the α4β2 and α6β2 subunits of the nucleus accumbens and the ventro-tegmental area) with enhancement of the “firing” of neurons which produce and release dopamine, increasing the additogenic potential of nicotine and making it more difficult for tobacco cessation attempts. Furthermore, it appears to potentiate the acute effects of nicotine on cognition by reinforcing the reward mechanism sought in smoking tobacco or nicotine products [16,17].

The effects of inhaled menthol as an additive to tobacco products and those alternatives to it, which are not only sensory, therefore produce epidemiological consequences on public health that we wish to summarise here. Those who approach cigarettes often start off with mentholated ones which, being perceived as pleasant and not very harmful, induce addiction in a short time and discourage attempts to free themselves from it. Through specific effects on the CNS, menthol reinforces addiction. It can increase the toxicity of smoke as it induces and allows for deeper inhalations. It also seems to inhibit the metabolism of NNAL, a carcinogenic component of tobacco smoke. Finally, it has an overall negative impact on public health, inducing an increase in the number of consumers and making it more difficult for the cessation of smoking. For all these reasons we want to underline once more how urgent are the strictest and most ambiguous government measures that can allow the complete elimination of the presence of menthol, in all its forms and quantities, in tobacco products and alternatives to it.

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