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.

Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming

“…Consistent with these observations, we found that chronic CA treatment leads to a futile metabolic cycle in subcutaneous fat cells which may constitute the key mechanism through which CA consumption leads to metabolic protection. Notably, a recent clinical trial with healthy subjects suggests that acute CA ingestion increases energy expenditure and postprandial fat oxidation, in which the CA dose is judged as “sensorially acceptable” by participants [18]. A pharmacokinetic study revealed that circulating levels of CA were detectable 20 h after oral delivery, indicating that consumption of cinnamon may be a feasible way to activate thermogenesis in subcutaneous fat and ultimately protect against obesity and metabolic disorders [19].…”

TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin

“…There are 27 human TRP family members pertaining to 6 groups: canonical (TRPC), melastatin (TRPM), vanilloid (TRPV), ankyrin (TRPA), mucolipin (TRPML), and polycystin (TRPP) (12). Although many TRP studies have focused on nociception (13, 14) and mechanosensation (15, 16), there are indications that certain TRP channels regulate energy metabolism and thermogenesis via nutritional intervention (17). Common dietary spices, such as chili (capsaicin), black pepper (piperine), clove (eugenol), garlic (allicin), cinnamon (cinnamaldehyde), or mint (menthol), have been shown to activate selected TRP channels (18), in certain instances impinging on transduction pathways common to nociception or temperature sensing (19, 20).…”

The Development of a Menthol Solution for Use during Sport and Exercise

“…Perception may be dependent upon physiological factors such as trigeminal chemosensitivity [33,34] and stratum corneum thickness [35], or environmental influences such as previous or habitual exposure to trigeminal agonists [36,37], e.g., regular use of mentholated products. Habitual menthol use may alter the threshold at which TRPM8 channels and the trigeminal nerve are stimulated [37][38][39][40], ultimately habituating thermal sensation [37,38].…”