Menthol

Menthol is a naturally occurring cyclic terpene alcohol contained in the essential oil of the Mentha species, which gives its distinctive taste and smell [1].

Menthol containing plants have a long history of use in herbal medicine, with peppermint used in Japan for more than 2000 years. The crystalline principle was first isolated in 1771 by Dutch botanist Gambius and through its continued use over the centuries, the industry now produces over 7000 tons annually, with a raw product value approaching $300 million [1].

Uses
Menthol has a huge variety of uses, from throat lozenges, pharmaceuticals, pain creams to pesticides, cosmetics, or flavouring agents [1, 2]. It is available for medicinal purposes prescribed and over the counter for conditions such as gastrointestinal disorders, common cold, respiratory conditions and musculoskeletal pain and is reported to have antipruritic, antiseptic, analgesic and cooling formulation properties [1]. Concentrations of menthol up to 16% have been approved by the FDA for external use and a safety profile has been well established [1].

Why does it have a cooling effect?
The mechanism of how menthol elicits a cool sensation has long been debated. In 1886, Goldcheider attributed the cold sensation to the stimulation of thermoreceptors but it was not till 2002 that 2 independent studies identified the thermosensitive cation channel, TRPM8 receptor. This channel was found to be activated by both menthol and thermal stimuli in the cool to cold range [1]. After application the menthol inhibits the Ca²⁺ currents through the channel and neuronal membranes, thus the cooling effect [3].

Poisonous to Humans?
The FDA considers menthol a safe substance and toxicities are rarely reported in literature [4]. However, ingestion of pure menthol can be dangerous, with over dosage possible with excess consumption. Lethal dosage is estimated to be 50-150mg/kg, with menthol in concentrations of 40% or more resulting in skin erythema and spontaneous burning [1]. Other adverse effects include dermatitis, cheilitis, mouth ulceration, abdominal pain, nausea, vomiting, bradycardia and tremor. Chronic exposure can occur after prolonged usage, and is associated with cutaneous, gastrointestinal and neurological manifestations [4]. No specific antidote is reported for menthol poisoning, and is treated with gastrointestinal decontamination, oral activated charcoal, with associated complications being managed accordingly [4].

Menthol cigarettes has also been linked to an increased likelihood of becoming addicted to smoking, as well as being more toxic than regular cigarettes [2]. Due to these and other findings, menthol cigarettes will now be phased out under new EU laws that will come into effect in May 2020, in the hope that it will deter younger generations taking up smoking.

Efficacy
Even though it is a widespread ingredient in over the counter medications, there is little evidence to support the supposed beneficial effects. A study in 2008 found that menthol had no effect on any of the spirometric measurements, and concluded it had no effect on objective measurement of flow but significantly increased the perception of nasal patency [2, 5]. However some evidence of the analgesic properties could be found which showed menthol could bind the K-opioid receptors and could possibly induce additional opioid analgesic effects [3]. More research is needed to further understand this reaction and its potency.

Studies have also found menthol to be effective against a variety of microorganisms, including both gram-positive, gram-negative bacteria, as well as fungi. This is supposedly through the perturbation of the lipid fraction of the microorganism, resulting in change of membrane permeability and leakage of intracellular materials [1].

Conclusions
So, Menthol might not actually make us breath any better when we have a cold or cool in the way we thought, but after 2000 plus years of use, I do not think it will be going anywhere from the medicinal cabinet. It will most likely not cause harm to humans, though the same cannot be said for microorganisms.

References:

[1] Patel T, Ishiuji Y, Yosipovitch G. 2007. Menthol: a refreshing look at this ancient compound. Journal of the American Academy of Dermatology 57:873-878. DOI: 10.1016/j.jaad.2007.04.008.

[2] Center PCNCP. 2012. Can Menthol Have Harmful Effects? . [Cited]. Available from: https://www.poison.org/articles/what-happens-with-swallowing-or-inhaling-too-much-menthol--174

[3] Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C. 2002. Menthol: a natural analgesic compound. Neuroscience Letters 322:145-148. DOI: https://doi.org/10.1016/S0304-3940(01)02527-7.

[4] Baibars M, Eng S, Shaheen K, Alraiyes AH, Alraies MC. 2012. Menthol Toxicity: An Unusual Cause of Coma. Case Reports in Medicine 2012:1-3. DOI: 10.1155/2012/187039.

[5] Kenia P, Houghton T, Beardsmore C. 2008. Does inhaling menthol affect nasal patency or cough? Pediatric Pulmonology 43:532-537. DOI: 10.1002/ppul.20797.

Images:

Peppermint: https://bynatureskincare.com/products/peppermint-essential-oil
Menthol Structure: https://pubchem.ncbi.nlm.nih.gov/compound/Menthol#section=2D-Structure
Menthol: https://en.wikipedia.org/wiki/Menthol