Capsaicin Consumption Research Articles

Capsaicin Shows Species and Strain-specific Activity: Investigation of the Antibacterial Effects on the Oral Pathogen Streptococcus mutans and the Oral Probiotics Streptococcus salivarius M18 and K12

Extensive research has investigated capsaicin (CAP), the primary bioactive compound in chili peppers, to explore its diverse pharmacological and physiological properties. Recently, the focus has shifted to understanding the potential effects of CAP on gut microbiota due to the strong link between gut bacterial profile and diet. However, there has been no research on the effects of CAP on oral microbiota. Therefore, our study aimed to explore the antibacterial effects of CAP on two oral probiotics, Streptococcus salivarius M18, and S. salivarius K12, along with the oral pathogen S. mutans. Previously, the anti-cancer activity of CAP had been demonstrated, and in accordance with these findings, here, we show its growth inhibitory activity on colorectal cancer cell lines. However, this study is the first to examine the impact of CAP on specific oral microorganisms while considering the oral consumption of CAP and the interconnectedness of the oral and gut microbiomes. The findings revealed that CAP exhibited antibacterial properties against the M18 strain at concentrations exceeding 100 µg/mL. Surprisingly, it did not show any growth-inhibitory effects on S. salivarius K12, even at a concentration of 2 mg/mL. Similarly, CAP did not inhibit the growth of S. mutans, a significant factor in dental caries. These results suggest that CAP's effects are species and strain-specific, indicating potential changes in the oral microbiota upon CAP consumption.

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

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.

P2-1 The association between capsaicin consumption and risk of developing gastrointestinal cancer: Systematic review

P2-1 The association between capsaicin consumption and risk of developing gastrointestinal cancer: Systematic review

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.

Analysis of the Ability of Capsaicin to Modulate the Human Gut Microbiota In Vitro.

Previous studies on capsaicin, the bioactive compound in chili peppers, have shown that it may have a beneficial effect in vivo when part of a regular diet. These positive health benefits, including an anti-inflammatory potential and protective effects against obesity, are often attributed to the gut microbial community response to capsaicin. However, there is no consensus on the mechanism behind the protective effect of capsaicin. In this study, we used an in vitro model of the human gut microbiota to determine how regular consumption of capsaicin impacts the gut microbiota. Using a combination of NextGen sequencing and metabolomics, we found that regular capsaicin treatment changed the structure of the gut microbial community by increasing diversity and certain SCFA abundances, particularly butanoic acid. Through this study, we determined that the addition of capsaicin to the in vitro cultures of the human gut microbiome resulted in increased diversity of the microbial community and an increase in butanoic acid. These changes may be responsible for the health benefits associated with CAP consumption.

Capsaicin and TRPV1 Channels in the Cardiovascular System: The Role of Inflammation.

Capsaicin is a potent agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel and is a common component found in the fruits of the genus Capsicum plants, which have been known to humanity and consumed in food for approximately 7000–9000 years. The fruits of Capsicum plants, such as chili pepper, have been long recognized for their high nutritional value. Additionally, capsaicin itself has been proposed to exhibit vasodilatory, antimicrobial, anti-cancer, and antinociceptive properties. However, a growing body of evidence reveals a vasoconstrictory potential of capsaicin acting via the vascular TRPV1 channel and suggests that unnecessary high consumption of capsaicin may cause severe consequences, including vasospasm and myocardial infarction in people with underlying inflammatory conditions. This review focuses on vascular TRPV1 channels that are endogenously expressed in both vascular smooth muscle and endothelial cells and emphasizes the role of inflammation in sensitizing the TRPV1 channel to capsaicin activation. Tilting the balance between the beneficial vasodilatory action of capsaicin and its unwanted vasoconstrictive effects may precipitate adverse outcomes such as vasospasm and myocardial infarction, especially in the presence of proinflammatory mediators.

Estimation of Dietary Capsaicinoid Exposure in Korea and Assessment of Its Health Effects

The consumption of capsaicinoids, the active components in chili peppers, has been associated with both positive and negative health effects, and the level of capsaicinoid exposure may be an important determinant. Dietary capsaicinoid exposure was estimated using a previously developed database for capsaicinoid content and a 24-h dietary recall dataset obtained from the Korea National Health and Nutrition Examination Survey. The estimated consumption level was evaluated to determine its potential effects on weight reduction and gastrointestinal distress. The estimated daily mean capsaicinoid intake was 3.25 mg (2.17 mg capsaicin), and most Koreans consumed 1–30 mg of capsaicinoids (0.67–20 mg capsaicin) in a day. No adverse effect of capsaicin consumption was reported other than abdominal pain. For long-term repeated consumption, 30 mg may be the maximum tolerable dose. However, the effects on body weight or energy balance were inconsistent in 4–12 week clinical studies conducted with various capsaicin doses (2–135 mg), which was likely due to the complex interplay between capsaicin dose, study length, and participant characteristics. Therefore, the capsaicin consumption of most Koreans was below the levels that may cause adverse effects. However, more long-term studies for the dose range of 2–20 mg are required to further characterize capsaicin’s health benefits in Koreans.

The Potential Link between Episodes of Diverticulitis or Hemorrhoidal Proctitis and Diets with Selected Plant Foods: A Case-Control Study.

Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case–control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.

Dose Escalation and Safety of Capsaicin for Cerebral Perfusion Augmentation: A Pilot Study.

Sphenopalatine ganglion (SPG) electrical stimulation has been studied in the setting of acute ischemic stroke to enhance collateral flow. Capsaicin poses an alternative to chemically stimulate the sphenopalatine ganglion. Therefore, the objective of this study was to determine the safety and effect of increasing doses of capsaicin upon serial transcranial Doppler markers of cerebral blood flow. We performed serial transcranial Doppler testing in 30 healthy volunteers divided into 5 equal groups. Capsaicin doses ranged from 33 to 165 μMol. We recorded peak systolic and end-diastolic velocities in the middle cerebral artery, arterial pressure, and perceived pungency in 5-minute intervals up to 20 minutes. We then calculated the mean velocity, the pulsatility index, and the cerebral blood flow index. The participants’ median age was 21 years (range, 5 years); all reported consumption of capsaicin in their diets. After and during the study, none reported side effects. Perceived pungency peaked at 5 minutes, and by the 20-minute mark, none perceived any pungency. All the tested doses produced the same pattern, consisting of augmentation of the middle cerebral artery mean velocity with the pulsatility index’s diminution. The effects peaked between the 5- and the 10-minute measurements and then returned to basal levels except for the 66-μMol doses, which produced a sustained effect. We found no correlation between perceived pungency and dose, but the middle cerebral artery mean velocity was strongly correlated with the dose administered. This study provides evidence supporting the safety and tolerability of oral capsaicin in a population of healthy volunteers. Capsaicin appears to produce effects similar to those of sphenopalatine ganglion electrical stimulation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04545892.

The correlation between chili pepper consumption and gastric cancer risk: A meta-analysis.

The correlation between chili pepper intake and gastric cancer (GC) risk has been controversial. We conducted a meta-analysis of 16 studies to provide updated evidence for this uncertainty. Medline, and China National Knowledge Infrastructure (CNKI) databases were searched to obtain all qualified literature related to pepper consumption and GC incidence before June 2020. Random effects models were adopted to integrate the relative risk of individual studies. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literature of each included study. Dose response meta-analysis was implemented through the one-stage robust error meta-regression (REMR) approach. 16 studies (8337 cases) were included in quantitative meta-analysis. The pooled odds ratio (OR) of GC for the highest versus the lowest category of chili consumption were 1.51 (95% confidence interval [CI]=1.02-2.00) for all countries, 2.05 (95% CI=1.15-2.95) for Mexican, 2.03 (95% CI =0.71-3.34) for Colombian, 1.92 (95% CI=1.21-2.64) for Asian and 0.48 (95% CI=0.24-0.72) for other countries. Dose-response meta-analysis showed that there was a positive linear correlation between the risk of GC and the daily frequency of chili consumption. Significantly increased consumption of chili pepper or capsaicin has the potential to increase the risk of gastric cancer, however, inconsistencies still exist in subgroup analysis between different regions.

An adaptive network model for pain and pleasure through spicy food and its desensitization

This paper aims to map out the adaptive causal pathways of processes underlying capsaicin consumption and the desensitization process of the TRPV1 receptor as a feedback loop together with pain and pleasure perception. In order to map out these causal capsaicin pathways, adaptive causal network modeling was applied, which is a way of modeling biological, neural, mental and social processes from an adaptive causal modeling perspective.

Nociceptors protect sickle cell disease mice from vaso-occlusive episodes and chronic organ damage.

Sickle cell disease (SCD) is a common hereditary hematologic disorder. SCD patients suffer from acute vaso-occlusive episodes (VOEs), chronic organ damage, and premature death, with few therapeutic options. Although severe pain is a major clinical manifestation of SCD, it remains unknown whether nociception plays a role in SCD pathogenesis. To address this question, we generated nociceptor-deficient SCD mice and found, unexpectedly, that the absence of nociception led to more severe and more lethal VOE, indicating that somatosensory nerves protect SCD mice from VOE. Mechanistically, the beneficial effects of sensory nerves were induced by the neuropeptide calcitonin gene-related peptide (CGRP), which acted on hematopoietic cells. Additionally, oral capsaicin consumption, which can activate somatosensory nerves by binding to TRPV1, dramatically alleviated acute VOE and significantly prevented chronic liver and kidney damage in SCD mice. Thus, the manipulation of nociception may provide a promising approach to treat SCD.

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer\u2019s disease-type pathology and cognitive deficits in APP/PS1 mice

Alzheimer’s disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice.

Mounting evidence has linked dietary capsaicin (CAP) consumption to the improvement of glucose homeostasis; however, the underlying mechanisms still need to be further elucidated. Male mice were fed a high-fat diet (HFD) with CAP administration for 8weeks, gut microbiota, bile acid (BA) profiles and markers for BA, and glucose metabolism were investigated. CAP improved glucose homeostasis partially by enhancing the secretion of glucagon-like peptide 1 (GLP-1). The gut microbiota was remodeled by CAP and was characterized by the increased abundance of Bacteroides genera, which is related with lithocholic acid (LCA) production. LCA is an endogenous agonist of Takeda G-protein coupled receptor 5 (TGR5); it may enhance GLP-1 secretion in intestinal L cells. Meanwhile, antibiotics experiment abolished the effects of CAP on glucose homeostasis and microbiota transplantation experiments demonstrated that the CAP-induced beneficial effects were transferable, indicating that the effects of CAP on glucose homeostasis were largely dependent on the gut microbiota. Additionally, we further identified that the improvements induced by CAP were attenuated by the antagonist of GLP-1 receptor, indicating that the activation of GLP-1 signaling contributes to the CAP-induced improvement in glucose homeostasis.

Induction and Prevention of Gastric Cancer with Combined Helicobacter Pylori and Capsaicin Administration and DFMO Treatment, Respectively.

Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes, including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e., capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2 g/kg/day) or not. Consequently, tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Moreover, we used 2-difluoromethylornithine (DFMO) in mice to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention by inhibiting IL-6. Accordingly, preventive measures such as reduced capsaicin consumption, H. pylori clearance, and DFMO treatment may lessen gastric cancer incidence.

Capsaicin alleviates lipid metabolism disorder in high beef fat-fed mice

This study was designed to evaluate the preventive mechanisms of capsaicin on beef fat-induced lipid metabolism disorder, oxidative stress and dysbacteriosis in mice. Mice were fed a control diet or a 30% beef-fat diet (BF) with or without 0.001% capsaicin for 12 weeks. The consumption of a BF with capsaicin effectively inhibited obesity and dyslipidemia in mice. Consumption of capsaicin improved the oxidative stress by reducing the hepatic malonaldehyde content and elevating the glutathionperoxidase activity. GC–MS analysis showed that the acetic acid content in the cecum was significantly increased by capsaicin supplementation. The enteric microflora species was not changed significantly by the consumption of capsaicin in BF-fed mice. The alleviation of dyslipidemia might be because capsaicin enhanced the antioxidant activity and elevated the enteric acetic acid levels in high beef fat-fed mice. Our results suggest that the ingestion of capsaicin might be an effective strategy for preventing beef fat-induced hyperlipidemia.

Putting out the fire – Efficacy of common beverages in reducing oral burn from capsaicin

Capsaicin is classically considered an irritant, due to the warming and burning sensations it elicits. Widespread consumption of chilis suggests many individuals enjoy this burn, but these sensations can be overwhelming if the burn is too intense. While substantial folklore exists on the ability of specific beverages to mitigate capsaicin burn, quantitative data to support these claims are generally lacking. Here, we systematically tested various beverages for their ability to reduce oral burn following consumption of capsaicin in tomato juice. Participants (n = 72, 42 women, 30 men) rated the burn of 30 mL of spicy tomato juice on a general Labeled Magnitude Scale (gLMS) immediately after swallowing, and again every 10 s for 2 min. On 7 of 8 trials, a test beverage (40 mL) was consumed after tomato juice was swallowed, including: skim milk, whole milk, seltzer water, Cherry Kool-Aid, non-alcoholic beer, cola, and water. Participants also answered questions regarding intake frequency and liking of spicy food. Initial burn of tomato juice alone was rated below “strong” but above “moderate” on a gLMS and continued to decay over the 2 min to a mean just above “weak”. All beverages significantly reduced the burn of the tomato juice. To quantify efficacy over time, area under the curve (AUC) values were calculated, and the largest reductions in burn were observed for whole milk, skim milk, and Kool-Aid. More work is needed to determine the mechanism(s) by which these beverages reduce burn (i.e., partitioning due to fat, binding by protein, or sucrose analgesia). Present data suggest milk is the best choice to mitigate burn, regardless of fat context, suggesting the presence of protein may be more relevant than lipid content.

Effects of Capsaicin on Biomimetic Membranes.

Capsaicin is a natural compound that produces a warm sensation and is known for its remarkable medicinal properties. Understanding the interaction between capsaicin with lipid membranes is essential to clarify the molecular mechanisms behind its pharmacological and biological effects. In this study, we investigated the effect of capsaicin on thermoresponsiveness, fluidity, and phase separation of liposomal membranes. Liposomal membranes are a bioinspired technology that can be exploited to understand biological mechanisms. We have shown that by increasing thermo-induced membrane excess area, capsaicin promoted membrane fluctuation. The effect of capsaicin on membrane fluidity was dependent on lipid composition. Capsaicin increased fluidity of (1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes, while it rigidified DOPC and cholesterol-based liposomes. In addition, capsaicin tended to decrease phase separation of heterogeneous liposomes, inducing homogeneity. We imagine this lipid re-organization to be associated with the physiological warming sensation upon consumption of capsaicin. Since capsaicin has been reported to have biological properties such as antimicrobial and as antiplatelet, the results will help unravel these biological properties.

Long-term consumption of capsicum annum (chilli pepper) and capsaicin diets suppresses pain perception and improves social behaviour of CD-1 mice

PurposeChilli pepper (Capsicum annum), an extensively cultivated vegetable, is commonly used to spice many dishes prepared in several parts of the world. It contains capsaicinoids. The most active amongst these capsaicinoids is capsaicin (8-methyl-N-vanillyl-6-nonenamide), which is neurogenic and so may affect nervous function. Therefore, the purpose of this paper is to investigate the effects of long-term consumption of chilli pepper and capsaicin diets on pain and social behaviour in CD-1 Swiss white mice.Design/methodology/approachIn total, 30 male mice were randomly assigned into three groups of ten mice each, namely, control, pepper-diet (20 per cent w/w) and capsaicin-diet (10 per cent w/w) groups. Tail immersion, hot plate and formalin tests were conducted to assess pain perception, while nesting behaviour test was used to evaluate the social behaviour of the mice.FindingsThe latency of tail flick of both the pepper and capsaicin groups were significantly longer (p < 0.01 and p < 0.001, respectively) compared to control. The hind paw lick frequency, duration and flinching of both the pepper and capsaicin groups were also significantly reduced compared to control. The nesting score of the capsaicin group was significantly higher (p < 0.01) compared to control. However, the nesting score for pepper group was significantly lower (p < 0.05) compared to capsaicin group.Originality/valueLong-term consumption of capsaicin and pepper diets suppressed pain and enhanced organized social behaviour in mice. One of the active principles responsible for the effects obtained with pepper on pain and social behaviour in mice may be capsaicin.