Back on July 6, 2000 we asked Dr. Ron Eccles (1994), a world authority on the chemistry and actions of menthol, isn't it true that just about all menthol's action (e.g., as a smooth muscle relaxant) is a result of inhibition of calcium dependent processes. His response: Yes I believe that menthol acts as a specific inhibitor to movement of calcium across cell membranes and in this way affects sensory nerve endings and smooth muscle. For more information click on menthol cold receptors and calcium..
The tobacco companies' marketing strategy has always been - smoke cigarettes for the taste and flavor and for the pure pleasure and enjoyment. Knowing perfecly well there was a need to get enough nicotine inhaled and absorbed to establish a dependence on cigarette smoking. In the 1920's the majority of tobaccos were highly acidic so when burned, smokers hesitated to inhale the smoke because of the irritating and harsh effects. Also, because of the acidic nature of the tobacco it was more difficult for nicotine to be absorbed. Besides the discovery of new varieties of tobacco that produced a more basic product, the introduction of menthol was a most worthwhile discovery that could counteract some of the negative features of smoking.
The use of mentholated products was initially promoted to offer an alternative to the heavy, harsh-tasting, hot and many-times unpleasant experiences with some non-mentholated products. The trend was to offer these mentholated cigarettes as a change-of-pace product. (Reid, 1993). In 1942 Brown and Williamson advertised that Kools would keep the head clear and/or give extra protection against colds (http://www.library.ucsf.edu/tobacco/docs/html/ 1700.04/1700.04.2.html). In 1973 the William Esty Company developed a Salem Cigarettes Sore Throat Seasonality Campaign (RJ Reynolds document #50378 2596). The objective was to encourage non-menthol smokers to switch to menthol during the winter sore throat season. The tobacco document included a questionnaire and a table of responses, showing that consumers perceive Salem to be good for the throat; half of those surveyed had used menthol cigarettes to provide relieve from scratchy throat.
Smokers compared with non-smokers have increased prevalence of chronic cough, chronic sputum production and wheezing. Also, the effect of smoking on both respiratory symptoms and lung function may be seen within a few years of the onset of regular smoking. In some smokers the rate of decline of forced expiratory volume leads to chronic airflow obstruction.
Smoking mentholated cigarettes may mask the impact of some of these problems. For more information on masking click Masking Respiratory Disease..
Menthol has been used widely for the treatment of nasal congestion but the
mechanism is still unknown. A study in healthy volunteers by Burrow et al.
(1983) demonstrated that inhalation of camphor, eucalyptus and menthol vapor had
no effect on nasal resistance to airflow, but exercise caused a marked decrease
in nasal resistance in the same group of subjects. The volunteers were asked if
their sensation of nasal airflow was improved after breathing the aromatics and
after exercise. One hundred percent of the subjects who breathed menthol
reported an increased sensation of nasal airflow whereas only 20% of subjects
reported improved airflow after exercise, despite a 70% decrease in nasal
resistance to airflow associated with exercise and no change in nasal resistance
after menthol. In another study (Eccles and Jones, 1983) total resistance to
airflow was measured in 31 subjects before and after five minute exposure to
menthol vapor. Menthol vapor had no consistent effect on nasal resistance but
the majority of subjects reported an increased sensation of nasal airflow and
the cooling effect of menthol. Eccles et al. (1990) demonstrated that the oral
administration of an 11mg menthol lozenge, in subjects suffering from nasal
congestion, caused a subjective sensation of improved airflow without any change
in nasal airway resistance. The increased nasal airflow caused by the inhalation
of menthol is believed to be due to the stimulation of cold receptors (Eccles,
1994). For more information click on menthol cold receptors
and calcium..
Twenty-one non-smoking subjects aged 19-46 years, with chronic mild asthma
were involved in this study. Each subject had only occasional asthmatic symptoms
which were controlled by use of a bronchodilator. Each subject measured the peak
expiratory flow rate (PEFR) twice a day (on awakening and on going to bed)
before inhalation of menthol, placebo or beta-agonists. In the placebo group
there was no change in the values for vital capacity (VC), forced expiratory
volume (FEV), change in PEFR and PC20 (a concentration that caused a 20%
decrease in FEV) . In contrast, menthol therapy did not significantly alter VC
or FEV but produced a decrease in the PEFR and an increase in PC20. In the
menthol group, patients had fewer wheezing episodes and less consumption of
bronchodilators. It was felt that menthol did not have any acute bronchodilatory
effects but did reduce airway hyperresponsiveness. In was concluded that menthol
might be beneficial in the treatment of mild asthma (Tamaoki et al., 1995). In
another study (Chiyotani et al., 1994) studied the effect of a poultice (a soft,
moist mass prepared by wetting various powders or other absorbent substances
with fluids, sometimes medicated, and usually applied hot to the surface)
containing menthol on the severity of bronchoconstriction and airway
hyperresponsiveness in asthma. Patients with mild to moderate asthma were
treated with the poultice for four weeks, during which period peak expiratory
flow (PEF) was measured by a peak flow meter and spirometry was performed. After
the treatment, diurnal variation of PEF decreased in five of six patients and
absolute values of PEF increased in three of six patients without apparent
adverse effects. Based on these findings the authors felt that menthol may be an
alternative drug in patients with asthma for not only decreasing
bronchoconstriction but also for improving airway hyperreponsiveness.
To evaluate the role L-menthol and mint oil as an anti-inflammatory drug, in
vitro investigations were performed using LPS-stimulated monocytes from healthy
volunteers. L-menthol significantly suppressed the production of each of three
inflammation mediators by monocytes in vitro. The results obtained with human
monocytes suggested preferable anti-inflammatory effects of L-menthol compared
to mint oil at therapeutically relevant concentrations supplied in enteric
coated capsules. The authors suggest that clinical trials be carried out to
determine the potential therapeutic efficacy of L-menthol for treatment of
chronic inflammatory disorders such as bronchial asthma (Juergens et al.,
1998)..
The use of menthol as an antitussive goes back over one hundred years when in
1890 a pharmacist, Lunsford Richardson, from Greensboro, North Carolina
developed a topical rub for the treatment of whooping cough (product later
became Vicks Vapo Rub). Despite the widespread use of menthol products to
relieve coughing there is very little literature available in the public domain
to support antitussive efficacy (Eccles, 1994).
Inhalation of menthol has been shown to inhibit respiration via stimulation
of upper airway cold receptors (For more information click on
Inhibit Respiration
and menthol may act to
inhibit cough via this mechanism. Respiratory reflexes such as cough are closely
linked to the brainstem centers regulating respiration and the general
inhibition of respiratory activity caused by menthol could also influence the
frequency and intensity of cough (Eccles, 1994). Menthol has also been shown to
influence the activity of cold receptors in the larynx and may influence the
activity of laryngeal sensory receptors involved in the cough reflex (influence
the activity of upper-airway sensory receptors and modulate respiratory
reflexes). The local anesthetic action of menthol seen at higher concentrations
may also play an important part in providing relieve from the common cold.
Menthol is a popular ingredient for steam inhalations taken for the treatment
of cough and is used as an expectorant (promoting the secretion or expulsion
from the mucous membranes of the air passages) to promote clearance of mucus
from the respiratory tract (Eccles, 1994).
Twenty healthy subjects received a cough challenge consisting of five
inhalations of citric acid from an air-driven dosimeter. The challenge was
repeated at hourly intervals for five hours. Five minutes before each challenge
subjects inhaled, in a randomized design, either menthol 75% in eucalyptus oil
or one of two placebos (pine oil or air). Menthol inhalation caused a reduction
in evoked cough when compared with either placebo (Morice et al., 1994).
Studies in guinea pigs also showed that menthol vapor reduced the frequency
of chemically induced cough (Laude et al., 1994).
Menthol given by steam inhalation to anesthetized rabbits augmented the
soluble mucus content and lowered the specific gravity of respiratory tract
fluid. This effect of menthol was produced by amounts of menthol which added no
detectable odor of menthol to the inspired air. The authors concluded that the
bronchomucotropic effects of menthol were due to direct local stimulation of
mucus secreting cells of the respiratory tract. The effect of menthol was dose
dependent as inhalation of high concentrations of menthol depressed both the
volume and mucus content of respiratory tract fluid (Boyd and Sheppard, 1969).
Five aromatic constituents of essential oils (cineole, citral, geraniol,
linaloul and menthol) were tested for antimicrobial activity against 18 species
of bacteria. Menthol inhibited the activity of 15 bacteria and seven fungi (
Pattnaik et al., 1997). Moleyar and Narasimham (1992) studied the antibacterial
activity of 15 essential oil components toward foodborne bacteria and
demonstrated that cinnamic aldehyde was the most active compound but that
menthol also had significant antibacterial activity.
T
Mentholated cigarettes having a minty smell counteract some of the
negative features of smoking. Smokers seem to always have a disgusting odor
about them and non-smokers constantly complain about the odor both in the air
they breath and the odor that gets in their clothing in the presence of
smokers.
Peppermint oil (main ingredient is menthol) is a carminative (relief of
gastric and intestinal discomfort caused by the collection of gases formed
during imperfect digestion) with potent antispasmodic properties (Eccles, 1994).
This activity probably makes menthol cigarettes the preferred after-dinner
smoke.
For information the uses of menthol click on Uses of Menthol..
For a list of menthol actions click on Menthol Actions
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Boyd EM and EP Sheppard, A bronchomucotropic action in rabbits from inhaled
menthol and thymol, Arch. Int. Pharmacodyn. 182(1): 206-214, 1969.
Burrow A R Eccles and AS Jones, The effect of camphor, eucalyptus and menthol
vapour on nasal resistance to airflow and nasal sensation, Acta Otolaryngol
96(1-2): 157-161, 1996.
Chiyotani A J Tamaoki, Effect of menthol on peak expiratory flow in patients
with bronchial asthma, Japanese J Chest Diseases 53(11): 949-953, 1994.
Eccles R MS Jawad and S Morris, The effects of oral administration of
(-)menthol on nasal resistance to airflow and nasal sensation of airflow in
subjects suffering from nasal congestion associated with the common cold, J.
Pharm. Pharmacol. 42(9): 652-654, 1990.
Eccles R, Menthol and Related Cooling Compounds, J. Pharm. Pharmacol. 46:
618-630, 1994.
Eccles R and AS Jones, The effect of menthol on nasal resistance to airflow,
J. Laryngol. Otol. 97(8): 705-709, 1997.
Juergens UR M Stober and H Vetter, The anti-inflammatory activity of
L-menthol compared to mint oil in human monocytes in vitro: a novel perspective
for its therapeutic use in inflammatory diseases, Eur. J. Med. Res. 3(12):
539-45, 1998.
Laude EA, AH Morice and TJ Grattan, The antitussive effects of menthol,
camphor and cineole in conscious guinea pigs, Pulm. Pharmacol. 7(3): 179-184,
1994.
Moleyar V and P Narasimham, Antibacterial activity of essential oil
components, Int. J. Food Microbiol. 16: 337-342, 1992.
Morice AH, AE Marshall, KS Higgins and TJ Grattan, Effect of inhaled menthol
on citric acid induced cough in normal subjects, Thorax 49(10): 1024-1026, 1994.
Pattnaik S, VR Subramanyan, M Bapaji and CR Kole, Antibacterial and antifugal
activity of aromatic constituents of essential oils, Microbios 89(358): 39-46,
1997.
Reid JR, A history of mentholated cigarettes
"This Spud's for you," 47th Tobacco Chemists'
Research Conference, October 18-21, 1993.
Tamaoki J, A Chiyotani, A Sakai, H Takemura and K Konno, Effect of menthol
vapor on airway
hyperresponsiveness in patients with mild asthma, Resp. Med. 89: 503-504,
1995.
Decongestant Activity
Chronic Inflammatory Disorders - Bronchial Asthma
Antitussive (capable of relieving coughing)
Bronchomucotropic (increase the amount of soluble mucus in the respiratory
tract)
Antibacterial Activity
Olfaction
Carminative Activity (inducing explusion of gas from stomach or
intestines)
References