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The Journal of Investigative Dermatology Jun 2018
Review
Topics: Administration, Cutaneous; Antipruritics; Chronic Disease; Cold Temperature; Humans; Menthol; Pruritus; Skin
PubMed: 29793625
DOI: 10.1016/j.jid.2018.04.008 -
European Journal of Sport Science Oct 2023We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance,... (Randomized Controlled Trial)
Randomized Controlled Trial
Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat.
We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat. Ten participants cycled at 70% maximal power output until exhaustion in 35°C and 20% relative humidity after application of (i) 5% isolated menthol, (ii) 5% menthol and 0.025% capsaicin co-application or (iii) placebo cream. Thermo-physiological responses were measured during exercise, with attentional focus and pain determined post-exercise on a 0-to-10 scale. Across the three conditions, time to exhaustion was 13.4 ± 4.8 min, mean ± SD infrared tympanic and skin temperature was 37.2 ± 0.6°C and 35.1 ± 1.2°C, respectively, and heart rate was 152 ± 47 bpm, with no changes between conditions (> 0.05). Perceived exertion was lower in the isolated menthol all other conditions (< 0.05, = 0.44). Thermal sensation was higher in menthol-capsaicin co-application isolated menthol (< 0.05, 1.1), while sweat rate was higher for capsaicin and menthol co-application compared to menthol (< 0.05, = 0.85). The median and interquartile range scores for pain were lower (< 0.05) in the menthol condition (8, 7-8) compared to both menthol and capsaicin (10, 9-10) and placebo (9, 9-10), which was coupled with a greater distraction (< 0.05) in the menthol condition (9, 7-10) compared to placebo (6, 5-7). Despite no performance effects for any topical cream application condition, these data reiterate the advantageous perceptual and analgesic role of menthol application and demonstrate no advantage of co-application with capsaicin.Topical application of isolated menthol cream to cold-sensitive areas of the body during exhaustive exercise in the heat, elicited reduced perception of pain and enhanced sensation of cooling.While this reduction in generally unpleasant feelings (i.e. pain and heat) were coupled with lower RPE scores in the menthol condition and could be considered beneficial, there was no apparent ergogenic effect in an exercise tolerance test.Co-application of capsaicin and menthol appeared to inhibit the positive sensory effects elicited by menthol.Isolated menthol can induce changes in cognitive processes related to pain and exertion, while also reducing thermal sensation; however, the decision to use menthol creams must be balanced with the limited performance or thermoregulatory effects reported herein during exercise in hot environments.
Topics: Humans; Body Temperature Regulation; Capsaicin; Exercise Tolerance; Hot Temperature; Menthol; Pain; Pain Perception; Thermosensing; Cross-Over Studies; Male; Female; Adult
PubMed: 37161852
DOI: 10.1080/17461391.2023.2211966 -
BMJ Open Apr 2022Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new...
INTRODUCTION
Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new smokers are initiating with menthol cigarettes, such that the prevalence of young adults menthol versus non-menthol smokers is increasing. Experimentation with menthol cigarettes is associated with progression to regular smoking and nicotine dependence. This ongoing clinical trial in young adult smokers measures appeal and the reinforcing value of smoking menthol versus non-menthol cigarettes and the impact of these variables on changes in smoking behaviour at a 6-month follow-up.
METHODS AND ANALYSIS
Reinforcement for menthol smoking is assessed in the laboratory using a validated behavioural economic choice task, and appeal is measured in the natural environment using ecological momentary assessment (EMA). Analyses will examine differences between menthol and non-menthol cigarette smoking on measures of subjective response in the laboratory and via EMA, and how subjective response mediates the association between menthol preference at baseline and smoking outcomes at follow-up.
ETHICS AND DISSEMINATION
This protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#10581). The findings will isolate the unique effects of menthol in smoking and will help inform regulatory decisions about the abuse liability of menthol cigarettes. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
NCT03953508.
Topics: Humans; Menthol; Smokers; Smoking; Tobacco Products; Tobacco Use Disorder; Young Adult
PubMed: 35487522
DOI: 10.1136/bmjopen-2021-058823 -
Veterinary Parasitology Sep 2022Nanocarriers of acaricidal compounds improve the bioavailability, absorption, and tissue distribution of active ingredients, releasing them in a slow, targeted way and...
Nanocarriers of acaricidal compounds improve the bioavailability, absorption, and tissue distribution of active ingredients, releasing them in a slow, targeted way and protecting them against premature degradation. Thus, this study aimed to develop formulations from solid lipid nanoparticles (SLN), or nanostructured lipid carriers (NLC) associated with cypermethrin (cip) + chlorpyrifos (chlo) and vegetable compounds (citral, menthol, or limonene). Particles were then characterised, and their efficacy was verified on R. microplus in comparison to nanoformulations without the plant-based compounds. Six different formulations were developed and characterised by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Formulations 1 (SLN+cyp+chlo+citral), 2 (SLN+cyp+chlo+menthol), 3 (SLN+cyp+chlo+limonene), 4 (NLC+cyp+chlo+citral), 5 (NLC+cyp+chlo+menthol) and 6 (NLC+cyp+chlo+limonene) had mean diameters from 286 to 304 nm; polydispersion from 0.16 to 0.18; zeta potential from -15.8 to -20 mV, concentration from 3.37 ± 0.24 × 10 to 5.44 ± 0.18 × 10 particles/mL and encapsulation efficiency (EE) > 98.01 % for all active ingredients. All formulations were evaluated for their acaricidal potential by the larval packet test (LPT) and compared with nanoformulations without the plant-based compounds. Formulations were also compared with positive (Colosso® at 512 µg/mL) and negative controls (distilled water and nanoparticles without active ingredients). The SLN (1, 2 and 3) and NLC (4, 5 and 6) formulations, at 7 µg/mL, resulted in 90.4 % , 75.9 % , 93.8 % , 100 % , 95.1 % and 72.7 % mortality. The data demonstrated that the addition of citral, menthol or limonene in the formulations improved their acaricide action against tick larvae. Except for formulation 4, for which it was not possible to determine lethal concentrations (LC). Formulations, 1, 2, 3, 5 and 6 reached LC and LC values of 3.3 and 7.2, 5.4 and 9.2, 4.0 and 8.1, 2.3 and 5.4 as well as 5.5 and 9.4 µg/mL, respectively. It was possible to encapsulate the active ingredients and characterise the lipid carrier systems. SLN and NLC protected the active ingredients against degradation in solution and increased the overall stability. A stabile solution is necessary for synthesizing commercial acaricidal products. It is hoped that these findings may contribute to new studies focused on the use of nanocarriers in tick formulations. By reducing the amount or concentration of active ingredients within commercial products, the risk of residues presents in food of animal origin or remaining in the environment is reduced. Nanocarriers help prevent these challenges, while still maintaining effective parasitic control. Utilizing a combination of natural and synthetic products can be part of integrated management solutions and can help overcome widespread acaricide resistance in populations of cattle ticks.
Topics: Acaricides; Animals; Limonene; Liposomes; Menthol; Nanoparticles; Phytochemicals; Rhipicephalus; Tick Control
PubMed: 35749843
DOI: 10.1016/j.vetpar.2022.109756 -
International Journal of Environmental... Jul 2021The use of electronic nicotine delivery systems (ENDS) among youth in the United States has increased rapidly in the past decade. Simultaneously, while youth cigarette...
Sociodemographic Patterns of Exclusive and Dual Use of ENDS and Menthol/Non-Menthol Cigarettes among US Youth (Ages 15-17) Using Two Nationally Representative Surveys (2013-2017).
The use of electronic nicotine delivery systems (ENDS) among youth in the United States has increased rapidly in the past decade. Simultaneously, while youth cigarette smoking has declined considerably, youth are still more likely to use menthol cigarettes than any other age group. We used nationally representative data on 15-17-year-olds from the Population Assessment of Tobacco and Health (PATH) Study and the National Youth Tobacco Survey (NYTS) (2013-2017) to better understand current cigarette (by menthol flavoring) and ENDS use in the US. We calculated weighted population prevalence estimates across years for multiple patterns of current cigarette and ENDS use (i.e., exclusive menthol cigarette, exclusive non-menthol cigarette, exclusive ENDS, dual ENDS and menthol cigarette, and dual ENDS and non-menthol cigarette) by sex, race/ethnicity, parental education level, household income, and homeownership. Overall, both exclusive menthol and non-menthol cigarette use declined from 2013-2017. Exclusive ENDS use increased, particularly among youth who were non-Hispanic White or had a higher socioeconomic status (measured by parental education, household income, and homeownership). Dual use of ENDS with either menthol or non-menthol cigarettes did not change significantly. Monitoring changes in these sociodemographic patterns will help inform future youth tobacco prevention strategies.
Topics: Adolescent; Cigarette Smoking; Electronic Nicotine Delivery Systems; Humans; Menthol; Tobacco Products; Tobacco Use; United States
PubMed: 34360077
DOI: 10.3390/ijerph18157781 -
Nicotine & Tobacco Research : Official... Oct 2021Menthol has been shown to target similar brain regions and neural receptors as nicotine, yet the association between menthol cigarette use and cognitive performance...
INTRODUCTION
Menthol has been shown to target similar brain regions and neural receptors as nicotine, yet the association between menthol cigarette use and cognitive performance remains unknown.
AIMS AND METHODS
This study examined differences in cognitive task performance between menthol (MS) and nonmenthol (NMS) cigarette smokers after acute cigarette consumption. Sixty white and black and/or African American, nonabstinent, MS (n = 30) and NMS (n = 30) were assessed presmoking and postsmoking their preferred cigarette on four computerized tasks: Continuous Performance Task (CPT; alerting attention), N-Back Task (working memory), Finger Tapping Task (motor control), and Apple Picker Task (reinforcement enhancement). Self-reported nicotine dependence and objective smoking topography measures were also compared between groups.
RESULTS
Initial unadjusted analyses showed a significant effect of cigarette type × time on CPT speed (p = .042), where MS improved while NMS group worsened in CPT speed after smoking. After controlling for baseline cigarette craving and cigarette nicotine levels, the effect of cigarette type × time for all cognitive outcomes was statistically nonsignificant (ps > .05). However, there remained a significant effect of cigarette type, where MS versus NMS had poorer CPT (p = .046) and N-Back Task accuracy (p = .006) but faster N-Back speed (p = .039). There were no statistically significant differences between groups on reinforcement enhancement, nicotine dependence, or smoking behavior outcomes (ps > .05).
CONCLUSIONS
Contrary to our hypotheses, results did not find a significant effect of cigarette type on the change in cognitive performance after acute smoking in nonabstinent smokers. Further studies are needed to clarify the specific pharmacological effects of nicotine and menthol on cognitive functioning.
IMPLICATIONS
The current study is the first to compare the potential enhancement of cognitive task performance after acute cigarette smoking between satiated menthol and nonmenthol cigarette smokers. Study results suggest that acute menthol cigarette use may not enhance cognitive function above and beyond nonmenthol cigarettes to increase dependence among menthol smokers. However, the contribution of other psychological factors (eg, craving, mood) and cigarette characteristics (eg, nicotine content) may be involved in cognitive function enhancement to perpetuate dependence and smoking persistence for menthol smokers.
Topics: Cognition; Humans; Menthol; Smokers; Task Performance and Analysis; Tobacco Products; Tobacco Use Disorder
PubMed: 34086950
DOI: 10.1093/ntr/ntab120 -
Nicotine & Tobacco Research : Official... Jan 2022Menthol cigarettes are popular among young adults and are disproportionately used by African American smokers. Menthol's minty and cooling sensations have been...
Affirming the Abuse Liability and Addiction Potential of Menthol: Differences in Subjective Appeal to Smoking Menthol Versus Non-Menthol Cigarettes Across African American and White Young Adult Smokers.
INTRODUCTION
Menthol cigarettes are popular among young adults and are disproportionately used by African American smokers. Menthol's minty and cooling sensations have been hypothesized to enhance the appeal and reinforcement of smoking; however, differences in menthol's subjective appeal across races have been inconsistent. This secondary data analysis examined differences in subjective appeal for smoking menthol versus non-menthol cigarettes between African American and White young adult smokers.
METHODS
Young adults (ages 18-24) recruited from Amazon Mechanical Turk (December 2018-January 2019) completed an online survey of tobacco use behavior. Past year smokers (n = 1726) answered questions about subjective responses to smoking (reward, satisfaction, throat hit, craving reduction, and aversion).
RESULTS
Significantly more African American (73.2%) compared to White (52.4%) smokers preferred menthol cigarettes (p < .001). Menthol smokers reported greater positive and negative subjective responses to smoking than non-menthol smokers. Positive and negative subjective response were both associated with greater smoking intensity and lower cigarette harm perceptions. Interactions of menthol preference and race on indices of subjective appeal also emerged. African American non-menthol smokers reported lower levels of satisfaction, reward, and craving reduction compared to White non-menthol smokers.
CONCLUSIONS
The relationship between menthol preference and subjective response to smoking differs by race. Menthol is rated as more appealing than non-menthol smoking, and appeal indices were linked to smoking intensity and lower harm perceptions, indicating greater abuse liability of menthol cigarettes. Policies that ban menthol cigarettes may have a particularly positive impact on the cigarette smoking of African American young adult smokers.
IMPLICATIONS
The FDA issued an Advanced Notice of Proposed Rule Making to examine the role menthol in tobacco products to inform regulations to restrict or ban flavors. This study showed that menthol smokers reported greater appeal to smoking than non-menthol smokers; and an interaction of race x menthol preference showed African American non-menthol smokers reported the lowest levels of appeal to smoking. Multiple indices of cigarette appeal were positively correlated with smoking intensity and lower cigarette harm perceptions, highlighting the addiction potential of menthol cigarettes. Findings suggest a menthol cigarette ban could help reduce tobacco use among young adults.
Topics: Adolescent; Adult; Black or African American; Humans; Menthol; Smokers; Smoking; Tobacco Products; Young Adult
PubMed: 34405884
DOI: 10.1093/ntr/ntab137 -
Applied and Environmental Microbiology Apr 2021More than 30,000 tons of menthol are produced every year as a flavor and fragrance compound or as a medical component. So far, only extraction from plant material and...
More than 30,000 tons of menthol are produced every year as a flavor and fragrance compound or as a medical component. So far, only extraction from plant material and chemical synthesis are possible. An alternative approach for menthol production could be a biotechnological-chemical process with ideally only two conversion steps, starting from (+)-limonene, which is a side product of the citrus processing industry. The first step requires a limonene-3-hydroxylase (L3H) activity that specifically catalyzes hydroxylation of limonene at carbon atom 3. Several protein engineering strategies have already attempted to create limonene-3-hydroxylases from bacterial cytochrome P450 monooxygenases (CYPs, or P450s), which can be efficiently expressed in bacterial hosts. However, their regiospecificity is rather low compared to that of the highly selective L3H enzymes from the biosynthetic pathway for menthol in species. The only naturally occurring limonene-3-hydroxylase activity identified in microorganisms so far was reported for a strain of the black yeast-like fungus sp. in South Africa. We have discovered additional fungi that can catalyze the intended reaction and identified potential CYP-encoding genes within the genome sequence of one of the strains. Using heterologous gene expression and biotransformation experiments in yeasts, we were able to identify limonene-3-hydroxylases from and Further characterization of the enzyme demonstrated its high stereospecificity and regioselectivity, its potential for limonene-based menthol production, and its additional ability to convert α- and β-pinene to verbenol and pinocarveol, respectively. (-)-Menthol is an important flavor and fragrance compound and furthermore has medicinal uses. To realize a two-step synthesis starting from renewable (+)-limonene, a regioselective limonene-3-hydroxylase enzyme is necessary. We identified enzymes from two different fungi which catalyze this hydroxylation reaction and represent an important module for the development of a biotechnological process for (-)-menthol production from renewable (+)-limonene.
Topics: Ascomycota; Aureobasidium; Biotransformation; Catalysis; Cytochrome P-450 Enzyme System; Fungal Proteins; Hydroxylation; Industrial Microbiology; Limonene; Menthol
PubMed: 33637576
DOI: 10.1128/AEM.02873-20 -
Journal of Dairy Science Mar 2021Stimulation of Ca absorption can counteract hypocalcemia at the onset of lactation. The plant bioactive lipid compound (PBLC) menthol is an agonist for nonselective...
Stimulation of Ca absorption can counteract hypocalcemia at the onset of lactation. The plant bioactive lipid compound (PBLC) menthol is an agonist for nonselective cation channels of the transient receptor potential (TRP) family. It acutely stimulated Ca absorption in ruminal epithelia of nonadapted animals ex vivo and caused higher plasma Ca concentrations in cows and sheep in vivo. To elucidate the pathway by which menthol feeding increases plasma Ca level, the present study aimed to investigate the long-term dose-dependent effects of dietary menthol-rich PBLC on Ca absorption and mRNA abundances of TRP channels in both rumen and jejunum. Twenty-four growing Suffolk sheep were equally distributed to a Con, PBLC-L, and PBLC-H group, which received 0, 80, and 160 mg/d of a menthol-rich PBLC. After 4 wk, ruminal and jejunal epithelia were analyzed for mRNA abundances of TRPA1, TRPV3, TRPV5-6, and TRPM6-8 genes. The Ca flux rates and electrophysiological properties of epithelia from rumen and mid-jejunum were measured in Ussing chambers in the presence and absence of mucosal Na. Acute changes in Ca flux rates were measured after mucosal application of 50 µM menthol. Ruminal epithelia had quantifiable transcripts of TRPV3 = TRPM6 >TRPM7 >TRPA1 with no difference among feeding groups. Jejunum had quantifiable transcripts of TRPM7 >TRPA1 ≥ TRPM6 ≥ TRPV6 >TRPV5, where TRPA1, TRPV5, and TRPV6 tended to decrease linearly with increasing PBLC dose. Absorptive net flux of Ca was detected only in the rumen, whereas jejunum showed a high passive permeability to Ca. Net flux rates of Ca in the rumen increased in a quadratic manner (highest in PBLC-L animals) and were systematically decreased with the omission of mucosal Na. Short-circuit current increased in both PBLC feeding groups compared with Con only in the rumen. Acute application of menthol-stimulated mucosal-to-serosal and net Ca flux rates only in ruminal epithelia with higher stimulation in PBLC-fed animals. We conclude that Ca transport is mainly active and transcellular in the rumen. It most likely involves TRPV3 that can be stimulated by menthol. Pre-feeding of menthol-rich PBLC enhances ruminal Ca absorption and sensitizes it to acute stimulation by menthol. By contrast, intestinal Ca absorption is not sensitive to menthol stimulation. Menthol could be used as a tool to enhance ruminal Ca absorption and to prevent hypocalcemia in dairy cows.
Topics: Animals; Calcium; Calcium, Dietary; Cattle; Female; Jejunum; Menthol; Rumen; Sheep
PubMed: 33358813
DOI: 10.3168/jds.2020-19372 -
American Journal of Physiology. Lung... Mar 2023E-cigarette consumption is under scrutiny by regulatory authorities due to concerns about product toxicity, lack of manufacturing standards, and increasing reports of...
E-cigarette consumption is under scrutiny by regulatory authorities due to concerns about product toxicity, lack of manufacturing standards, and increasing reports of e-cigarette- or vaping-associated acute lung injury. In vitro studies have demonstrated cytotoxicity, mitochondrial dysfunction, and oxidative stress induced by unflavored e-cigarette aerosols and flavoring additives. However, e-cigarette effects on the complex lung parenchyma remain unclear. Herein, the impact of e-cigarette condensates with or without menthol flavoring on functional, structural, and cellular responses was investigated using mouse precision cut lung slices (PCLS). PCLS were exposed to e-cigarette condensates prepared from aerosolized vehicle, nicotine, nicotine + menthol, and menthol e-fluids at doses from 50 to 500 mM. Doses were normalized to the glycerin content of vehicle. Video-microscopy of PCLS revealed impaired contractile responsiveness of airways to methacholine and dampened ciliary beating following exposure to menthol-containing condensates at concentrations greater than 300 mM. Following 500 mM menthol-containing condensate exposure, epithelial exfoliation in intrabronchial airways was identified in histological sections of PCLS. Measurement of lactate dehydrogenase release, mitochondrial water-soluble-tetrazolium salt-1 conversion, and glutathione content supported earlier findings of nicotine or nicotine + menthol e-cigarette-induced dose-dependent cytotoxicity and oxidative stress responses. Evaluation of PCLS metabolic activity revealed dose-related impairment of mitochondrial oxidative phosphorylation and glycolysis after exposure to menthol-containing condensates. Taken together, these data demonstrate prominent menthol-induced pulmonary toxicity and impairment of essential physiological functions in the lung, which warrants concerns about e-cigarette consumer safety and emphasizes the need for further investigations of molecular mechanisms of toxicity and menthol effects in an experimental model of disease.
Topics: Animals; Mice; Nicotine; Electronic Nicotine Delivery Systems; Menthol; Respiratory Aerosols and Droplets; Lung; Flavoring Agents
PubMed: 36692165
DOI: 10.1152/ajplung.00222.2022