Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects

Abstract

Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin.

Trial registration: ClinicalTrials.gov NCT02193438.

Figure 1. Impact of Givaudan Cooling flavor (QB-113-979-5) on hTRPA1, hTRPV1 and hTRPM8.

By calcium imaging the effect and specificity of the cooling flavor has been evaluated on cells expressing hTRPA1, hTRPV1 or hTRPM8. The cooling flavor activates specifically hTRPM8 in a dose-dependent way. Data are represented by the mean of relative fluorescence ± s.e.m, n = 6. EC50 =~0.07% (=half maximal effective concentration).

Figure 2

Trial design (A) and facial regions of interest analyzed by facial thermography (B).

Figure 3

Effect of treatment on Energy expenditure (A,D), fat oxidation (B,E) and CHO oxidation (C,F). (A–C) Data distribution averaged over 10 min +- SD. (D–F) Comparison of treatment AUC (time standardized) +– SE. Cinnamaldehyde significantly increases AUC of energy expenditure compared to placebo (D). Both cinnamaldehyde and capsaicin significantly increase fat oxidation AUC compared to placebo (E). (*p < 0.05; Unadjusted p-values computed using mixed model, n = 16–18).

Figure 4

Effect of treatment on heart rate. Comparisons of different treatments with placebo at 0, 5, 10 and 15 minutes after ingestion. Data over 1 minute were aggregated and expressed as effect size +– SE. No significant differences are observed between placebo and any treatment, all p-value being >0.221 (p-values were computed using a mixed linear model, n = 16–18).

Figure 5

Nose (A) and left cheek (B) temperature. Comparisons of different treatments with placebo at 0, 5, 10 and 15 minutes after ingestion. Data over 1 minute were aggregated and expressed as effect size +− SE. (*Adjusted p-value < 0.05; **Adjusted p-value < 0.001; p-values were computed using a mixed linear model while adjusted for multiplicity using Holm’s method, n = 16–18).

Figure 6

Evaluation of sample sensory intensity from questionnaire.