L-Menthol

The herbs of Mentha canadensis L.

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.[Pubmed:9889172]

Eur J Med Res. 1998 Dec 16;3(12):539-45.

The anti-inflammatory efficacy of monoterpenes is still unknown. In order to evaluate the potential role of L-Menthol and mint oil as an anti-inflammatory drug, preclinical in vitro-investigations were performed using LPS-stimulated monocytes from healthy volunteers. Arachidonic acid metabolism was assessed by measuring LTB subset4 and PGE subset2 as indicators for both the lipoxygenase and the cyclooxygenase pathways respectively. In addition, the anti-inflammatory effects of the two terpenes on IL-1beta production were analysed. - L-Menthol significantly suppressed the production of each of the three inflammation mediators by monocytes in vitro. LTB subset4 decreased by -64.4 +/- 10%, PGE subset2 by -56.6 +/- 8%, and IL-1beta by -64.2 +/- 7% respectively at L-Menthol concentrations within the presumed therapeutic range of about 10 superset-7 g/ml. In contrast, mint oil had a bimodal effect on PGE subset2 production: lower concentrations of 10 superset-10 to 10 superset-8 g/ml increased PGE subset2 up to 6-fold compared to baseline but concentrations of 10 superset-7 g/ml suppressed PGE subset2 production by approximately 50%. Mint oil had similar effects on LTB subset4 and IL-1beta as its main constituent, L-Menthol, although the degree of suppression was by comparison smaller at lower concentrations. Paraffin oil, which served as a solvent, did not affect arachidonic acid metabolism and IL-1beta production. - These results obtained with human monocytes suggest preferable anti-inflammatory effects of L-Menthol compared to mint oil at therapeutically relevant concentrations supplied in enteric coated capsules. Therefore, clinical trials investigating the potential therapeutic efficacy of L-Menthol for treatment of chronic inflammatory disorders such as bronchial asthma, colitis and allergic rhinitis seem worthwhile.

Antiperistaltic effect and safety of L-menthol sprayed on the gastric mucosa for upper GI endoscopy: a phase III, multicenter, randomized, double-blind, placebo-controlled study.[Pubmed:21353674]

Gastrointest Endosc. 2011 May;73(5):932-41.

BACKGROUND: GI peristalsis during GI endoscopy commonly requires intravenous or intramuscular injection of antispasmodic agents, which sometimes cause unexpected adverse reactions. OBJECTIVE: Our ultimate goal was to evaluate whether the antiperistaltic effect of L-Menthol-based preparations facilitates endoscopic examinations in a clinical setting. DESIGN: Multicenter, randomized, double-blind, placebo-controlled study. SETTING: Six Japanese referral centers. PATIENTS AND INTERVENTION: A total of 87 patients scheduled to undergo upper GI endoscopy were randomly assigned to receive 160 mg of L-Menthol (n=45) or placebo (n=42). Both treatments were sprayed endoscopically on the gastric mucosa. The degree of gastric peristalsis was assessed by an independent committee. MAIN OUTCOME MEASUREMENTS: The proportion of subjects with no peristalsis 90 to 135 seconds after administration and at the end of the endoscopic examination (complete suppression of gastric peristalsis). Other outcomes were the proportion of subjects with no or mild peristalsis (adequate suppression of gastric peristalsis) and the ease of intragastric observation as evaluated by the endoscopist who performed the procedure. RESULTS: Gastric peristalsis was completely suppressed in 35.6% (21.9, 51.2) of the L-Menthol group compared with only 7.1% (1.5, 19.5) of the placebo group (P<.001). In the L-Menthol group, 77.8% (62.9, 88.8) (35/45 subjects) of the subjects had no or mild peristalsis at the completion of endoscopy. Minor peristalsis interfered with intragastric examination in only 1 of these 35 patients (2.9%). The incidence of adverse events did not differ significantly between the groups (P=.512). LIMITATION: Small sample size. CONCLUSIONS: During upper GI endoscopy, L-Menthol sprayed on the gastric mucosa significantly suppresses peristalsis with minimal adverse drug reactions compared with placebo. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00742599.).

Relieving thermal discomfort: Effects of sprayed L-menthol on perception, performance, and time trial cycling in the heat.[Pubmed:25943672]

Scand J Med Sci Sports. 2015 Jun;25 Suppl 1:211-8.

L-Menthol stimulates cutaneous thermoreceptors and induces cool sensations improving thermal comfort, but has been linked to heat storage responses; this could increase risk of heat illness during self-paced exercise in the heat. Therefore, L-Menthol application could lead to a discrepancy between behavioral and autonomic thermoregulatory drivers. Eight male participants volunteered. They were familiarized and then completed two trials in hot conditions (33.5 degrees C, 33% relative humidity) where their t-shirt was sprayed with CONTROL-SPRAY or MENTHOL-SPRAY after 10 km (i.e., when they were hot and uncomfortable) of a 16.1-km cycling time trial (TT). Thermal perception [thermal sensation (TS) and comfort (TC)], thermal responses [rectal temperature (Trec ), skin temperature (Tskin )], perceived exertion (RPE), heart rate, pacing (power output), and TT completion time were measured. MENTHOL-SPRAY made participants feel cooler and more comfortable and resulted in lower RPE (i.e., less exertion) yet performance was unchanged [TT completion: CONTROL-SPRAY 32.4 (2.9) and MENTHOL-SPRAY 32.7 (3.0) min]. Trec rate of increase was 1.40 (0.60) and 1.45 (0.40) degrees C/h after CONTROL-SPRAY and MENTHOL-SPRAY application, which were not different. Spraying L-Menthol toward the end of self-paced exercise in the heat improved perception, but did not alter performance and did not increase heat illness risk.

L-menthol improves adenoma detection rate during colonoscopy: a randomized trial.[Pubmed:24573731]

Endoscopy. 2014 Mar;46(3):196-202.

BACKGROUND AND STUDY AIMS: Colonoscopy is one of the most reliable methods for the detection of colorectal neoplasms. However, colonic peristalsis during colonoscopy results in some neoplastic lesions being hidden from view and commonly requires an intravenous or intramuscular injection of antispasmodic agents, which may sometimes causes unexpected adverse reactions. The aim of this study was to evaluate the efficacy of L-Menthol spray as an antiperistaltic agent and its effect on adenoma detection. PATIENTS AND METHODS: This was a prospective, randomized, single-blind placebo-controlled trial. A total of 226 patients who were scheduled to undergo colonoscopy were randomly assigned to receive either 20 mL of 1.6 % L-Menthol (n = 118) or placebo (n = 108). Both treatments were sprayed locally onto the colonic mucosa via an endoscope. The adenoma detection rate (ADR) and the proportion of patients with no peristalsis were the primary and secondary outcomes, respectively. RESULTS: The ADR was significantly higher in the L-Menthol group than in the placebo group (60.2 % vs. 42.6 %; P = 0.0083). The proportion of patients with no peristalsis after treatment with L-Menthol was significantly higher than in the placebo group (71.2 % vs. 30.9 %; P < 0.0001). There were no adverse effects in either group. CONCLUSIONS: The results suggest that the suppression of colonic peristalsis by L-Menthol sprayed directly onto the colonic mucosa improves the ADR. CLINICAL TRIAL REGISTRATION: ID: UMIN 000007972.

(-)-Menthol is a key component of peppermint oil that binds and activates transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable nonselective cation channel, to increase [Ca2+]i. Antitumor activity.

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