Dietary Capsaicin Research Articles

Racial Specificity In The Hypotensive Effects Of Dietary Capsaicin: A Spicy Conclusion

Racial Specificity In The Hypotensive Effects Of Dietary Capsaicin: A Spicy Conclusion

Effects of dietary capsaicin supplementation on growth performance, blood profile and carcass and meat quality of finishing pigs.

This study was conducted to determine the effects of capsaicin (CAP) on productive performance, blood profile, intestinal morphology, carcass and meat quality of growing-finishing pigs. Two experimental diets were offered to 36 crossbred barrows: basal diet (0% CAP) and basal diet with CAP at 0.02%. Each experimental group consisted of 18 pigs, with six replications (three each). Supplementation of CAP at 0.02% decreased average daily feed intake (ADFI; p = 0.003) and feed cost/gain (FCG; p = 0.056), increased return on investment (ROI; p = 0.052) and increased gain:feed ratio (p = 0.037) during the growing period. There was no effect of CAP on the growth rate. The blood urea nitrogen (BUN) and nitrogen (N) levels in faeces tended to decrease (p = 0.093 and p = 0.087), whereas the basophil level increased with CAP supplementation (p = 0.029). In addition, dietary CAP supplementation decreased crypt depth (p = 0.022) and tended to increase the villus height/crypt depth ratio in the segment of the jejunum (p = 0.084). Backfat (BF) thickness (p = 0.047) was reduced by supplementing CAP. Whereas the protein content increased with CAP supplementation (p = 0.021). Using CAP in the diet of growing pigs increased the pH at 6 h post-mortem (p = 0.046) and tended to increase the springiness value (p = 0.078) of the meat. In terms of meat color, CAP supplementation increased the yellowness (p = 0.029). Supplemental CAP improves gut morphology and blood profiles, consequently promoting productive performance as well as carcass and meat quality.

Preconceptional capsaicin intervention mitigates negative effects of paternal obesity on metabolic characteristics in male offspring upon high-fat diet challenge

The activation of brown adipose tissue by cold exposure in paternal mice has been reported to improve the metabolic health of offspring. Notably, dietary components for activating BAT have drawn considerable attention owing to their high feasibility for human trials. Therefore, here the potential metabolic improving effects of dietary capsaicin intervention on diet-induced obese paternal mice and their offspring were measured. The results support that paternal preconceptional capsaicin intervention not only elicited the anticipated enhancement of brown fat activity in obese paternal mice, but also improved the metabolic profiles in male offspring evidenced by their elevated resistance to high-fat diet challenge. Moreover, changes in sperm DNA methylation and small non-coding RNA profile were noted in paternal mice with capsaicin intervention, though additional investigation is needed to further delve into the mechanisms. In summary, paternal dietary intervention activating BAT could represent a promising strategy for enhancing the metabolic health of offspring.

Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder

The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer.CLQ_5di4C7NjAvrz19eKZiVideo

Capsaicin supplementation prevents western diet-induced hyperleptinemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice

Background: Endoplasmic reticulum (ER) stress implicated in leptin resistance in the diet-induced obesity, which can accelerate the development of atherosclerosis forms the background of this study.
 Objective: This study aimed to investigate the effect of capsaicin on hyperleptinema by inhibiting ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a western diet (WD).
 Design: ApoE -/- mice were assigned one of three experimental diets: WD (60% kcal from fat, n = 10), WD + 0.015% capsaicin (n = 10, w/w), and WD + 1% PBA (n = 10, w/w) for 12 weeks.
 Results: In metabolic parameters, supplementation of dietary capsaicin displayed marked reduction of body weight gain and adipose tissue weight, plasma leptin, total cholesterol, and hepatic triglyceride levels without change in the plasma insulin level compared with WD fed ApoE-/- mice after 12 weeks. Capsaicin supplementation also attenuated the protein expression of ER stress markers such as eukaryotic translational initiation factor 2α and C/EBP homology protein in the liver, as well as glucose-related protein 78 localization in the aorta, indicating that capsaicin inhibits diet-induced hyperleptinemia in part by regulating the protein expression involved in ER stress.
 Conclusion: Capsaicin, therefore, may have potential as a therapeutic agent for individuals with diet-induced hyperleptinemia

Dietary Intake of Capsaicin and Its Association with Markers of Body Adiposity and Fatty Liver in a Mexican Adult Population of Tijuana.

Background: Capsaicin (CAP) is the main chemical component responsible for the pungency (burning pain) of the chili plant (capsicum spp.), whose metabolic functions include energy balance and fatty acid oxidation. The aim of this study is to analyze the association of dietary capsaicin consumption with markers of adiposity and fatty liver in a Mexican adult population. Methods: This cross-sectional/analytical study recruited 221 subjects aged 18 to 65 years who were resident in the city of Tijuana, Baja California, Mexico. The daily CAP intake was analyzed through a validated chili/CAP consumption questionnaire. Anthropometric and biochemical measurements were performed following standardized protocols. Adjusted Pearson's correlations were applied to analyze the association of CAP with adiposity and fatty liver markers. Results: In this study, the daily average consumption of CAP was 152.44 mg. The dietary CAP consumption positively correlated with BMI (r = 0.179, p = 0.003), hip circumference (r = 0.176, p = 0.004) and body adiposity index (r = 0.181, p = 0.001. Likewise, the daily CAP intake positively correlated with hepatic steatosis index (r = 0.158, p = 0.004), fatty liver index (r = 0.141, p = 0.003) and lactate dehydrogenase (r = 0.194, p = 0.016) after statistical settings. Conclusions: The results of this study suggest positive associations between dietary CAP consumption and the markers of body adiposity and fatty liver in a Mexican adult population.

Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.

The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.

The Vanilloid (Capsaicin) Receptor TRPV1 in Blood Pressure Regulation: A Novel Therapeutic Target in Hypertension?

Today's sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by capsaicin of TRPV1-expressing sensory afferents evokes a drop in blood pressure by triggering the Bezold-Jarisch reflex. In hypertensive rats, capsaicin reduces blood pressure. Conversely, genetic ablation of the TRPV1 receptor results in elevated nocturnal (but not diurnal) blood pressure. These observations imply a therapeutic potential for TRPV1 activation in hypertensive patients. Indeed, in a major epidemiological study involving 9273 volunteers, dietary capsaicin was found to lower the risk for hypertension. New research indicates that the mechanism of action of capsaicin on blood pressure regulation is far more complex than previously thought. In addition to the well-recognized role of capsaicin-sensitive afferents in blood pressure regulation, TRPV1 seems to be expressed both in endothelial cells and vascular smooth muscle. This review aims to evaluate the therapeutic potential of TRPV1-targeting drugs in hypertensive patients.

Sex differences in estimates of cardiac autonomic function using heart rate variability: effects of dietary capsaicin.

Heart rate variability (HRV) estimates the autonomic nervous system (ANS) influence on the heart and appears sex-specific. Sensory afferents exhibit sex-specificity; although, it is unknown if Capsaicin, an agonist for transient receptor potential vanilloid channel-1 (TRPV1), alters cardiac ANS activity in a sex-dependent manner, which could be important given the predictive nature of HRV on risk of developing hypertension. Thus, we explored if there was sex-specificity in the effect of capsaicin on estimated cardiac ANS activity. HRV was measured in 38 young males (M: n = 25) and females (F: n = 13), in a blinded-crossover design, after acute ingestion of placebo or capsaicin. Resting HR, RR-interval, root-mean-square of successive differences (RMSSD), natural log-transformed RMSSD (LnRMSSD), standard deviation of n-n intervals (SDNN), number of pairs of successive n-n intervals differing by > 50ms (NN50), and percent NN50 (PNN50) were obtained using standard techniques. Significant sex differences were observed in mean HR (M: 59 ± 9.3 vs. F: 65 ± 12 beats/min, p = 0.036, η2 = 0.098), minimum HR (M: 47 ± 8.3 vs. F: 56 ± 12 beats/min, p = 0.014, η2 = 0.124), and NN50 (M: 177 ± 143 vs. F: 29 ± 17, p < 0.001, η2 = 0.249). There was a significant interaction of sex*treatment (p = 0.02, η2 = 0.027) for RMSSD, where males increased (78 ± 55 vs. 91 ± 64ms), and females decreased (105 ± 83 vs. 76 ± 43ms), placebo vs. capsaicin. This controlled study recapitulates sex differences in HR and HRV, but revealed a sexual dimorphism in the parasympathetic response to capsaicin, perhaps due to differing TRPV1-afferent sensitivity, highlighting a potential mechanism for differential regulation of hemodynamics, and CVD risk, and should beconsidered in future studies.

Capsaicin shapes gut microbiota and pre-metastatic niche to facilitate cancer metastasis to liver

Dietary factors are fundamental in tumorigenesis throughout our lifetime. A spicy diet has been ambiguous on the development of cancers, especially in the study of colon cancer metastasis. Here, we utilized a mouse metastasis model to test the potential role of capsaicin in influencing metastasis. Long-term continuous administration of capsaicin diet (300 mg/kg) to mice promotes the formation of liver pre-metastatic niche to facilitate the metastasis of colon cancer cells. Bacteria translocation to liver is clearly observed. Capsaicin increases intestinal barrier permeability and disrupts gut vascular barrier by altering the composition of gut microbiota. Capsaicin not only changes the abundance of mucin-related bacteria like Akkermanisa and Muribaculaceae, but also bacteria involved in bile acids metabolism. Dysregulated bile acids profile is related to the recruitment of natural killer T (NKT) cells in pre-metastatic niche, primary bile acid α-Muricholic acid can enhance the recruitment of NKT cells, while secondary bile acids Glycoursodeoxycholic acid and Taurohyodeoxycholic acid impair the recruitment of NKT cells. These findings reveal long term consumption of capsaicin increases the risk of cancer metastasis through modulating the gut microbiota. Capsaicin (300 mg/kg) disrupts gut barrier and promotes the translocation of bacteria to liver, while altered bile acids metabolism affects the recruitment of NKT cells in liver, forming a pre-metastatic niche and promoting cancer metastasis.

Does sex influence near-infrared spectroscopy-derived indicators of microvascular reactivity and the response to acute dietary capsaicin.

Endothelial dysfunction is associated with cardiovascular disease development, nitric oxide (NO) deficiencies, and may be limb or sex-specific. Prior in vitro work indicated that the transient receptor potential vanilloid channel-1 (TRPV1) is expressed in human arteries and the TRPV1 agonist capsaicin alters vasodilation in an endothelium-dependent manner; however, it is unknown if this translates in vivo or is limb or sex-dependent. Therefore, we sought to determine if there was limb or sex-specificity in the effect of capsaicin on microvascular function using near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (StO2) reperfusion slope. In a blinded placebo-controlled crossover design, 45 young males (M: n=25) and females (F: n=20), the reperfusion slopes of the forearm and quadriceps were assessed, and a urine sample obtained to assay for nitrate/nitrite (NOx) concentrations and antioxidant capacity after acutely ingesting placebo or capsaicin. Under placebo, females had greater reperfusion rates in both the forearm (M: 0.44±0.24 vs. F: 0.98±0.46%/sec; p=0.002, d=-1.50) and quadricep (M: 0.86±0.31 vs. F: 1.17±0.43%/sec; p=0.010, d=-0.85). Capsaicin decreased microvascular responsiveness in the forearm of females (placebo: 0.98±0.45 vs. capsaicin: 0.84±0.45%/sec) as compared to males (placebo: 0.45±0.24 vs. capsaicin: 0.38±0.16%/sec, interaction p<0.001, η2=0.475). There was a sex*treatment interaction for NOx concentrations, where males increased (placebo: 21.13±12.83 vs. capsaicin: 23.82±13.34μM), while females decreased (placebo: 22.78±14.40 vs. capsaicin: 14.43±10.01μM; p=0.037, η2=0.042). Using NIRS to assess microvascular function, there is apparent limb and sex-specificity, and, for the first-time, document that acute oral capsaicin alters reperfusion slope in a sexually divergent manner.

Effects of Dietary Capsaicin and Yucca schidigera Extracts as Feed Additives on Rumen Fermentation and Microflora of Beef Cattle Fed with a Moderate-Energy Diet

Capsaicin (CAP) and Yucca schidigera extract (YSE) are two types of plant extracts that can change rumen fermentation. This study was conducted to investigate whether supplementation of beef cattle diets with CAP and YSE for 90 days would affect rumen fermentation and microflora. Forty-five healthy Angus steers (initial body weight = 510.54 ± 41.27 kg) were divided into three groups: control (CON), CAP, and YSE. Ammonia nitrogen (NH3-N) and total volatile fatty acid (TVFA) concentrations were significantly higher in the YSE group than in the CON group and significantly lower in the CAP group than in the CON group. At the phylum level, YSE increased the relative abundances of Bacteroidota and Patescibacteria and reduced that of Bacillota. At the genus level, CAP and YSE both increased the relative abundances of genera subordinate to Bacteroidota and decreased the relative abundances of genera subordinate to Bacillota. Our study shows that YSE and CAP have different effects on rumen fermentation and microflora after long-term supplementation.

Dietary Supplementation of Capsaicin Enhances Productive and Reproductive Efficiency of Chinese Crossbred Buffaloes in Low Breeding Season.

The present study investigated the role of dietary capsaicin (CPS) supplementation on milk yield (liters/head) and milk composition (total solids, lactose, albumin, protein, fat, milk urea nitrogen (MUN), somatic cell count (SCC) and somatic cell score (SCS), serum metabolites (lipoprotein esterase (LPL) and aspartate aminotransferase (AST)), and reproductive physiology (follicular development, estrus response, ovulation and pregnancy) following synchronization during the low breeding season. One hundred (n = 100) crossbred buffaloes were randomly assigned to four dietary groups consisting of CPS supplementation dosages (0, 2, 4 or 6 mg/kg of total mixed ration; TMR) as CPS-0 (n = 26), CPS-2 (n = 22), CPS-4 (n = 25) and CPS-6 (n = 27), respectively, in a 30-day feed trial. The results revealed that the CPS-4 group of buffaloes had a better estrus rate (72%) along with improved (p < 0.05) ovulatory follicle diameter (13.8 mm), ovulation rate (68%) and pregnancy rate (48%) compared to other treatment groups. Milk yield improved (p < 0.05) in CPS-4 supplemented buffaloes after day 20 of the trial, comparatively. There was a significant effect (p < 0.05) of milk sampling day (day 30) on total milk solids, lactose, milk protein and MUN levels, whereas lactose, MUN, SCC and SCS were influenced by supplementation dosage (CPS-4). Glucose levels were affected in buffaloes by sampling time (artificial insemination (AI) and 50-day post-AI) and CPS-dose (CPS-4 and CPS-6), respectively. LPL level changed in CPS-2 and CPS-4 groups at AI time and 50 days after AI. In addition, the AST level was different in CPS-4 at AI time and 50 days after AI. Therefore, our data suggest that a medium dose (~4 mg/kg of TMR) of CPS provided a better response in the form of milk yield, milk composition, serum metabolites and reproductive performance in crossbred buffaloes during the low breeding season.

Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?

Today's sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.

Nociceptive Nerves Facilitate Hematopoietic Stem/Progenitor Cell Homing to Bone Marrow By Tuning Microcirculation

The homing process of hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) is critical for engraftment after BM transplantation (BMT). Nociceptive nerves in BM reportedly regulate the mobilization of HSPCs from BM by directly supplying calcitonin gene-related peptide (CGRP) to HSPCs. However, it remains unclear whether nociceptive nerves control HSPC dynamics other than egress from BM, e.g., homing to BM. Here, we show that nociceptive nerves facilitate HSPCs homing to BM by controlling microcirculation. To assess the effects of CGRP on the BM microenvironment, we immunostained BM sections of mice and found that BM arteries, but not sinusoids, expressed CGRP receptors. We next employed intravital imaging system that visualized calvarial BM vessels and combined it with the transcalvarial administration (TCA), a method that enables manipulation of local BM microcirculation. TCA of CGRP receptor antagonist constricted BM arteries and decreased sinusoidal flux and shear stress, that impeded transendothelial migration (TEM) of transplanted HSPCs into BM, suggesting that CGRP released from nociceptive nerves supports local BM microcirculation and facilitates TEM of transplanted HSPCs into BM. In addition, systemic administration of CGRP receptor antagonist and pharmacological and genetic ablation of nociceptive nerves significantly decreased the homing efficiency of transplanted HSPCs to BM. Moreover, CGRP administration restored homing efficiency in nociceptive denervated-mice, and improved homing efficiency of wild-type mice. We next examined whether the improved homing efficiency of HSPCs with CGRP administration was mediated via arteries or via hematopoietic cells. CGRP is sensed by a heterodimeric CGRP receptor composed of calcitonin receptor-like receptor (CALCRL) and receptor activity modifying protein 1 (RAMP1), and hematopoietic cells reportedly express both CALCRL and RAMP1. We prepared Ramp1-/- mice to examine the homing efficiency of Ramp1-deficient hematopoietic cells. We found that the homing efficiency of hematopoietic cells from Ramp1-/- mice was not impaired upon transplantation into wild-type recipients. These results suggest that CGRP acts on the BM microenvironments, not on hematopoietic cells, to improve the homing efficiency. To determine the relationship between homing control by nociceptive nerves and survival after transplantation, we analyzed survival after BMT in mice in which nociceptive nerves were denervated. We found that pharmacological and genetic denervation of nociceptive nerves in recipient mice significantly reduced survival after BMT. Finally, to determine whether the intake of spicy food that activates nociceptive nerves enhances the efficiency of BMT, mice were fed with food containing capsaicin and subjected to homing experiments. HSPC homing efficiency to BM of mice fed with capsaicin diet was significantly improved compared to that of mice with normal diet. This study reveals a novel function of nociceptive nerves in regulating BM microcirculation and HSPC homing, and suggests that nociceptive nervous system could be a new therapeutic target for improving BMT efficiency.

Dietary Capsaicin Reduces Chemically Induced Rat Urinary Bladder Carcinogenesis.

Capsaicin (CAP) is the compound responsible for pungency in chili peppers, presenting several biological properties. But its general safety and effectiveness in the context of carcinogenesis has not been fully clarified. Thus, the present study evaluated whether dietary CAP modifies the development of urothelial lesions induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male Sprague-Dawley rats. Animals were randomly allocated into 6 groups: G1 - treated with 0.05% BBN in drinking water (weeks 1-12) and received a balanced diet (weeks 1-20); G2 and G3-treated with BBN (weeks 1-12) and received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G4 and G5- only received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G6 - only received a balanced diet (weeks 1-20). At the end of week 20, the incidence and types of urothelial lesions, proliferating cell nuclear antigen (PCNA) labeling index, and matrix metalloproteinases (MMP) 2 and 9 activities were analyzed. A significant reduction was observed in the incidence and multiplicity of simple (p = 0.020 and p = 0.011) and nodular/papillary (p = 0.030 and p = 0.003) hyperplasias and papillomas/carcinomas (p = 0.023 and p = 0.020), epithelial proliferation (p = 0.007) and in the activity of the intermediate form of MMP-2 (p < 0.001) and pro-MMP-9 activities (p < 0.002), in BBN + 0.02% CAP (G3) group in comparison to BBN (G1) group. Capsaicin intake per se did not alter body weight, liver and kidney weights, urothelial histology or serum biochemical parameters. Thus, dietary CAP was safe and showed a protective effect against rat BBN-induced urothelial carcinogenesis.

Capsaicin for Weight Control: "Exercise in a Pill" (or Just Another Fad)?

Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has been a culinary staple for thousands of years and is generally deemed safe when consumed in hedonically acceptable, restaurant-like doses. This review critically evaluates the available experimental and clinical evidence for and against capsaicin as a weight control agent and comes to the conclusion that capsaicin is not a magic “exercise in a pill”, although there is emerging evidence that it may help restore a healthy gut microbiota.

Capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption by blocking TRPV4 channels in healthy and colitic mice

Although capsaicin has been studied extensively as an activator of the transient receptor potential vanilloid cation channel subtype 1 (TRPV1) channels in sensory neurons, little is known about its TRPV1-independent actions in gastrointestinal health and disease. Here, we aimed to investigate the pharmacological actions of capsaicin as a food additive and medication on intestinal ion transporters in mouse models of ulcerative colitis (UC). The short-circuit current (Isc) of the intestine from WT, TRPV1-, and TRPV4-KO mice were measured in Ussing chambers, and Ca2+ imaging was performed on small intestinal epithelial cells. We also performed Western blots, immunohistochemistry, and immunofluorescence on intestinal epithelial cells and on intestinal tissues following UC induction with dextran sodium sulfate. We found that capsaicin did not affect basal intestinal Isc but significantly inhibited carbachol- and caffeine-induced intestinal Isc in WT mice. Capsaicin similarly inhibited the intestinal Isc in TRPV1 KO mice, but this inhibition was absent in TRPV4 KO mice. We also determined that Ca2+ influx via TRPV4 was required for cholinergic signaling–mediated intestinal anion secretion, which was inhibited by capsaicin. Moreover, the glucose-induced jejunal Iscvia Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain- and amiloride-sensitive colonic Isc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain- and amiloride-sensitive Isc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its beneficial anti-colitic action.

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Effects of Capsaicin on the Hypoglycemic Regulation of Metformin and Gut Microbiota Profiles in Type 2 Diabetic Rats.

Dietary capsaicin (CAP), the main irritant component in pepper, can reduce the incidence of diabetes, while metformin (MET) is a first-line oral hypoglycemic drug. The purpose of this study was to investigate whether CAP on the hypoglycemic effect of MET is pertinent to gut microbiota. The glucose and insulin tolerance of diabetic rats were monitored. The glycolipid metabolism was analyzed by detecting blood biochemical parameters. Liver pathological changes were observed by Hematoxylin eosin (HE) staining. The inflammatory cytokines and intestinal tight junction proteins were detected by RT-qPCR and Western blot. 16S rRNA sequencing was employed to analyze gut microbiota profiles. The results showed that CAP and MET co-treatment could significantly reduce fasting blood glucose, improve glucose tolerance, lessen liver injury and inflammatory infiltration, down-regulate inflammatory cytokines and up-regulate intestinal tight junction proteins in diabetic rats by comparing it with MET monotherapy. Moreover, CAP and MET co-treatment altered gut microbiota profiles by regulating microbials' abundances such as Akkermansia. In conclusion, CAP showed the significant hypoglycemic effect of MET and remodulated gut microbiota profiles in diabetic rats.