title: The absorption and metabolism of a single L-menthol oral versus skin administration: Effects on thermogenesis and metabolic rate.
abstract: We investigated the absorption and metabolism pharmacokinetics of a single L-menthol oral versus skin administration and the effects on human thermogenesis and metabolic rate. Twenty healthy adults were randomly distributed into oral (capsule) and skin (gel) groups and treated with 10 mg kg(-1) L-menthol (ORALMENT; SKINMENT) or control (lactose capsule: ORALCON; water application: SKINCON) in a random order on two different days. Levels of serum L-menthol increased similarly in ORALMENT and SKINMENT (p > 0.05). L-menthol glucuronidation was greater in ORALMENT than SKINMENT (p < 0.05). Cutaneous vasoconstriction, rectal temperature and body heat storage showed greater increase following SKINMENT compared to ORALMENT and control conditions (p < 0.05). Metabolic rate increased from baseline by 18% in SKINMENT and 10% in ORALMENT and respiratory exchange ratio decreased more in ORALMENT (5.4%) than SKINMENT (4.8%) compared to control conditions (p < 0.05). Levels of plasma adiponectin and leptin as well as heart rate variability were similar to control following either treatment (p > 0.05). Participants reported no cold, shivering, discomfort, stress or skin irritation. We conclude that a single L-menthol skin administration increased thermogenesis and metabolic rate in humans. These effects are minor following L-menthol oral administration probably due to faster glucuronidation and greater blood menthol glucuronide levels.
authors.affiliation: FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece.
authors.forename: Angelica
authors.initials: A
authors.lastname: Valente
authors.affiliation: Department of Exercise Science, Chatham University, Pittsburgh, PA, 15232, USA.
authors.forename: Andres E
authors.initials: AE
authors.lastname: Carrillo
authors.affiliation: Centre of Toxicology Science and Research, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Manolis N
authors.initials: MN
authors.lastname: Tzatzarakis
authors.affiliation: Centre of Toxicology Science and Research, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Elena
authors.initials: E
authors.lastname: Vakonaki
authors.affiliation: Centre of Toxicology Science and Research, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Aristidis M
authors.initials: AM
authors.lastname: Tsatsakis
authors.affiliation: Human and Environmental Physiological Research Unit, University of Ottawa, Ontario, Canada.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Kenny
authors.affiliation: School of Physical Education and Exercise Science, University of Thessaly, Greece; Institute of Sport, Faculty of Education, Health, and Wellbeing, University of Wolverhampton, WV1 1LY, UK.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Koutedakis
authors.affiliation: School of Physical Education and Exercise Science, University of Thessaly, Greece.
authors.forename: Athanasios Z
authors.initials: AZ
authors.lastname: Jamurtas
authors.affiliation: FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece; Human and Environmental Physiological Research Unit, University of Ottawa, Ontario, Canada. Electronic address: andreasflouris@gmail.com.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Flouris
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005965:Glucuronates / Q000097:blood / Q000493:pharmacokinetics; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008610:Menthol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010465:Perception; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects*; D022722:Thermogenesis / Q000187:drug effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D005965:Glucuronates; D008610:Menthol; C044963:menthol glucuronide
keywords: Brown adipose tissue; Cardiovascular diseases; Energy consumption; Non-shivering thermogenesis; Partitional calorimetry; UCP1