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Background/Objectives: Capsinoids are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, this study aimed to investigate the effects of capsinoids on adiposity and biomarkers of cardiac oxidative stress in obese rats induced by a high-fat diet. Methods: Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After the characterization of obesity (week 19), some of the obese animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury, and biomarkers of oxidative stress were determined. Results: The treatment did not reduce obesity-induced adiposity but was efficient in reducing cholesterol levels. Capsinoid treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capsinoids did not reduce the increase in the advanced oxidation of protein products and carbonylated proteins caused by obesity in cardiac tissue. In addition, obese rats treated with capsinoids presented high levels of malondialdehyde and greater antioxidant enzyme activity compared to untreated obese rats. Conclusions: In conclusion, treatment with capsinoids increases antioxidative enzyme activity and prevents obesity-induced cardiac injury without positively modulating body fat accumulation and cardiac oxidative biomarkers. [ABSTRACT FROM AUTHOR]

Background/Objectives: Capsinoids are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, this study aimed to investigate the effects of capsinoids on adiposity and biomarkers of cardiac oxidative stress in obese rats induced by a high-fat diet. Methods: Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After the characterization of obesity (week 19), some of the obese animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury, and biomarkers of oxidative stress were determined. Results: The treatment did not reduce obesity-induced adiposity but was efficient in reducing cholesterol levels. Capsinoid treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capsinoids did not reduce the increase in the advanced oxidation of protein products and carbonylated proteins caused by obesity in cardiac tissue. In addition, obese rats treated with capsinoids presented high levels of malondialdehyde and greater antioxidant enzyme activity compared to untreated obese rats. Conclusions: In conclusion, treatment with capsinoids increases antioxidative enzyme activity and prevents obesity-induced cardiac injury without positively modulating body fat accumulation and cardiac oxidative biomarkers.

Capsinoids may exert ergogenic effects on resistance exercises. However, the acute effects of capsinoids on neuromuscular performance in humans are unknown. Here, we aimed to investigate the acute effects of dihydrocapsiate on lower- and upper-body neuromuscular performance parameters in resistance-trained individuals. 25 young adults (n = 6 women; age = 26 ± 3 years; body mass index = 24.3 ± 2.8 kg/m²) with= 1-year resistance training experience were included in this triple-blind (participants, intervention researchers, and data analysts were blinded), placebo-controlled, crossover study. Lower- and upper-body ballistic strength (countermovement jump [CMJ] height and bench press throw [BPT] peak velocity), maximum dynamic strength (estimated 1 repetition maximum in squat and bench press [BP]), and strengthendurance (mean set velocity [squat] and number of repetitions to failure [bench press]) were assessed in 2 independent sessions (=7 days separation). Participants ingested 12 mg of dihydrocapsiate or placebo 30 min before each trial. We found no significant differences between dihydrocapsiate and placebo conditions in ballistic strength, (CMJ height 33.20 ± 8.07 vs 33.32 ± 7.85 cm; BPT peak velocity 2.82 ± 0.77 vs 2.82 ± 0.74 m/s) maximal dynamic strength (estimated squat 1RM: 123.76 ± 40.63 vs 122.66 ± 40.97 kg; estimated BP 1RM: 99.47 ± 43.09 vs 99.60 ± 43.34 kg), and strength-endurance (squat mean set velocity 0.66 ± 0.07 vs 0.66 ± 0.05 m/s; number BP repetitions to failure 13.00 ± 3.56 vs 13.00 ± 4.78) (all P = 0.703). We conclude that dihydrocapsiate does not acutely improve neuromuscular performance in trained young adults. [ABSTRACT FROM AUTHOR]

As a bioactive component in Capsicum species, capsaicin is a compound of hot chili peppers which is known as the main substance responsible for the spiciness of these fruits. Besides its taste and physiological effects, it exhibits good antioxidant activity in food matrix and antimicrobial activity against foodborne pathogens and viruses. Considering its low stability and bioaccessibility, and also regarding its irritation, the entrapment methods of capsaicin are fully developed. To compensate the limitations of capsaicin, various encapsulation methods have been used so far, including coacervation, emulsion, spray chilling, and liposomal delivery. Capsaicin has been widely used as a flavoring and preservative agent in food formulations and even as an active compound in packaging film and functional foods. This review provides an overview of the techno-functional properties, stabilization procedures, and burgeoning usages of capsaicin in the latest studies of the food sector. So, it may introduce new windows for the application of this compound. [ABSTRACT FROM AUTHOR]

Background Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure (EE) and fat oxidation (FATox), yet whether they can modulate those parameters during exercise conditions remains poorly understood. We hypothesized that dihydrocapsiate (DHC) ingestion would increase EE and specifically FATox during an acute bout of aerobic exercise at FATmax intensity (the intensity that elicits maximal fat oxidation during exercise [MFO]) in men with overweight/obesity. Since FATmax and MFO during aerobic exercise appear to be indicators of metabolic flexibility, whether DHC has an impact on FATox in this type of population is of clinical interest. Methods A total of 24 sedentary men (age = 40.2 ± 9.2 years-old; body mass index = 31.6 ± 4.5 kg/m2 [n = 11 overweight, n = 13 obese]) participated in this randomized, triple-blinded, placebo-controlled, crossover trial (registered under ClinicalTrials.gov Identifier no. NCT05156697). On the first day, participants underwent a submaximal exercise test on a cycle ergometer to determine their MFO and FATmax intensity during exercise. After 72 hours had elapsed, the participants returned on 2 further days (≥ 72 hours apart) and performed a 60 min steady-state exercise bout (i.e. cycling at their FATmax, constant intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized. Respiratory gas exchange was monitored by indirect calorimetry. Serum marker concentrations (i.e. glucose, triglycerides, non-esterified fatty acids (NEFAs), skin temperature, thermal perception, heart rate, and perceived fatigue) were assessed. Results There were no significant differences (P > 0.05) between DHC and placebo conditions in the EE and FATox during exercise. Similarly, no significant changes were observed in glucose, triglycerides, or NEFAs serum levels, neither in the skin temperature nor thermal perception across conditions. Heart rate and perceived fatigue did not differ between conditions. Conclusions DHC supplementation does not affect energy metabolism during exercise in men with overweight/obesity.

Background: Approximately 30% of the global population is affected by obesity. Traditional non‐surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography—computed tomography—(PET‐CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity. Sources of material: PubMed Central, Europe PMC, Medline. Findings: In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non‐shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the β3‐adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation. Conclusions: The use of currently available BAT‐activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option. [ABSTRACT FROM AUTHOR]

Background: Brown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as b-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss. Methods: We systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults. Results: A total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as b-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials. Conclusion: Though the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy. [ABSTRACT FROM AUTHOR]

BackgroundBrown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss.MethodsWe systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults.ResultsA total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as β-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials.ConclusionThough the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy.

The outcomes of the earlier trials are controversial concerning the effect of Capsaicinoids/Capsinoids on thermogenesis. We carried out this systematic review and meta-analysis to examine the effect of Capsaicinoids/Capsinoids on thermogenesis indices including resting metabolic rate (RMR) and respiratory quotient (RQ) in healthy adults. An electronic literature search was conducted between 1990 and 2019, using the following databases: PubMed, Web of Sciences, Scopus, Cochrane Central Register of Controlled Trials, and EMBASE. Placebo-controlled clinical trials were considered as eligible papers. Effect sizes were pooled using weighted mean difference (WMD), with a random-effects model. Of the 4,092 articles, 13 studies were included in the meta-analysis. Pooled effect sizes revealed that compared with placebo, Capsaicinoids/Capsinoids significantly increased RMR (WMD: 33.99 Kcal/day, 95% CI: 15.95, 52.03; I2 : 0%, p = .94), energy expenditure, and fat oxidation. It also significantly lessened RQ (WMD: -0.01, 95% CI: -0.02, -0.01; I2 : 5.4%, p = .39) and carbohydrate oxidation. Moreover, intervention in capsule form for longer duration had a more considerable influence on RMR than comparative groups. We observed moderate improvement in RMR, RQ, and fat oxidation following supplementation with Capsaicinoids/Capsinoids. However, further high-quality studies are required to clarify the thermogenic properties of Capsaicinoids/Capsinoids. [ABSTRACT FROM AUTHOR]

Capsaicinoids are acid amides of C9–C11 branched-chain fatty acids and vanillylamine and constitute important chemical compounds of Capsicum annuum together with their non-pungent analogs (capsinoids) which have an impressive list of health benefit properties (i.e., analgesia, anti-obesity, thermogenic, cardiovascular, gastrointestinal, antioxidant, anti-bacterial, anti-virulence, anti-inflamatory, anti-diabetic, inhibits angiogenesis, and improves glucose metabolism). In this review, the state of art on how capsaicinoids are affected by different pre- and postharvest factors is discussed together with their biological activity. For instance, high light intensity and heat treatments may reduce capsaicinoid content in fruits probably due to the loss of activity of capsaicin synthase (CS) and phenylalanine ammonia lyase (PAL). The pungency in peppers varies also with environment, genotype or cultivar, node position, fruiting and maturity stages, nitrogen and potassium contents. As the fruit mature, capsaicinoid levels increase. Fruits from the second node tend to have higher accumulation of pungency than those of other positions and the pungency decreases linearly as the node position increase. Sodium hydroxide treatment reduces the pungency of pepper fruit as it hydrolyzes and modifies one of the features (vanillyl group, the acid-amide linkage and alkyl side chain) of capsaicin molecule. Salt and water stress increase PAL and capsaicin synthase activity and increase the capsaicinoid accumulation in fruit, by negatively regulating peroxidase activity at appropriate levels. Future research must be directed in better understanding the changes of capsinoids during pre and post-harvest management, the causal drivers of the loss of activity of the aminotransferase gene (pAMT) and if possible, studies with genetically modified sweet peppers with functional pAMT. Available data provided in this review can be used in different agricultural programs related to developing new cultivars with specific pungency levels. The contents of capsaicinoids and capsinoids in both fresh fruits and marketed products are also of remarkable importance considering the preferences of certain niches in market where higher added-value products might be commercialized. [ABSTRACT FROM AUTHOR]

Besides capsaicin (CAP), capsiate (CAT) is now recognized as an important secondary metabolite of pepper (Capsicum spp.) for use as a health food, dietary supplement, and pharmaceutical. However, genetic resources for high levels of CAT are scarce worldwide. Sources of variation are needed to develop new commercial pepper varieties with high levels of CAT. This study was primarily conducted to evaluate high CAT yields with or without CAP. Moreover, two DNA markers, which were associated with CAT and CAP, were used to identify the presence of these two secondary metabolites. Results indicated that the accession KKU-P31146 contained the highest levels of CAT (505.3 µg/g DW) without Sum CAPs among the 19 tested accessions. Although the KKU-P62268 pepper accession showed the highest Sum CATs (3794.1 µg/g DW), it contained lower levels of CAT than KKU-P31146. The dCAPS (p-AMT) molecular marker amplified a DNA fragment of 269 bp, whereas a 1670 bp DNA fragment was not amplified by the SCAR (Pun1) molecular marker. In addition, the genotypic data from the two known molecular markers were associated with CAT and Sum CAPs in all tested accessions. In particular, this association was clearly observed in KKU-P31146. The novel discovery here is that KKU-P31146 should be considered as a new source for breeding high-CAT accessions due to its high CAT and no CAP. An obvious association between the CAT-related genotypic and phenotypic traits of KKU-P31146 indicated that the two known markers are useful for the selection of pepper accessions with the target trait. [ABSTRACT FROM AUTHOR]

Objectives: Performance in runningbased sport depends on the ability to perform repetitive high intensity muscle contractions. Previous studies have shown that capsaicin analog (CAP) (i.e. Capsiate) supplementation may improve this performance. The purpose of this study was to investigate the acute effect of CAP supplementation on short (400 m) and middle distance (3000 m) running time-trial performance, maximum heart rate (HR), and rate of perceived exertion (RPE). Methods: Twelve physically active men completed four randomized, double-blind trials: CAP condition (12 mg) or a placebo condition. Forty-five minutes after supplementation, the participants performed a 400- or 3000-meter running time trial. Time (in seconds) was recorded. HR was analyzed at rest and immediately post-exercise, and RPE was collected immediately after exercise. Results: For both the 400 m time-trial (CAP = 66.4 + 4.2 sec vs Placebo = 67.1 + 4.8 sec, p = 0.046) and the 3000 m time-trial (CAP = 893.9 ± 46.8 sec vs Placebo = 915.2 ± 67.6 sec, p = 0.015), the time in seconds was significantly less in the CAP compared to placebo conditions. There were no statistically significant differences for HR and RPE in any condition. Conclusion: In summary, acute CAP supplementation improved 400 m and 3000 m running time-trial performance in a distance-dependent way but without modifying the HR and RPE. [ABSTRACT FROM AUTHOR]

Capsaicinoids, which cause a hot sensation when eaten, are uniquely present in pepper (Capsicum sp.) and are biosynthesized by combining vanillyl amine with branched fatty acids. A mutation in the gene encoding putative aminotransferase (pAMT)—the enzyme that normally biosynthesizes the capsaicinoid precursor vanillyl amine—leads instead to the biosynthesis of vanillyl alcohol, which combines with branched fatty acids to form capsinoids. Here, we report a method for increasing the capsaicinoid and capsinoid contents using quantitative trait locus (QTL) alleles involved in capsaicinoid biosynthesis in the pericarps of extremely spicy peppers. QTLs for capsinoid contents were detected on chromosome 6 and 10 using an F2 population from ‘SNU11–001’ and ‘Bhut Jolokia (BJ)’ (‘SJ’). ‘SNU11–001’ contains high capsinoid contents and ‘BJ’ contains high capsaicinoid contents in both the placenta and pericarp. These QTLs overlapped QTL regions associated with pungency in the pericarp. ‘BJ’ was crossed also with ‘Habanero’ (‘HB’), which contains capsaicinoids mainly in the placenta, and the resulting (‘HJ’) F2 and F3 offspring with ‘BJ’ genotypes were selected based on QTL markers and the pericarp pungency phenotype. Similarly, F2 and F3 offspring with high capsinoid contents in the pericarp were selected in ‘SJ’ with reference to ‘BJ’ genotypes at the QTLs. Through continuous self-pollination, ‘SJ’ and ‘BJ’ lines with high capsinoid and capsaicinoid contents, respectively, in both the placenta and pericarp were developed. This study is the first to show that lines containing high levels of capsinoids and capsaicinoids can be bred using pericarp capsaicinoid biosynthesis genes.

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Introduction: In previous study, a capsinoids intake would enhance the energy expenditure and fat oxidation in humans. If a capsinoids (CSN) can stimulate fat oxidation and spare glycogen stores following exercise resulting in delaying exercise-induced fatigue. The purpose of the study was to investigate the effect of acute oral CNS supplementation on fat oxidation, muscle glycogen and fatigue during exercise. Methods: Ten healthy subjects (age 20.6 ± 0.3 years; height 171.3 ± 2.4 cm; weight 67.0 ± 3.4 kg; BMI 21.1 ± 0.6 kg/m2; V ‧ O2 max 46.4 ± 2.4 ml/kg/min) completed a crossover study design with CNS and placebo trials and performed a single bout of cycling exercise challenge with glycogen depletion protocol for 70 minutes, separated a 7-d washout period. All subjects consumed 30 mg CSN or placebo with light breakfast before exercise challenge. Blood samples were measured before meal and during exercise. Expired gas samples were collected during exercise. Simultaneously, muscle biopsy samples were obtained from vastus lateralis before and immediately after exercise. Results: Plasma glycerol and non-esterified fatty acid, at 40 and 60 min during exercise were significantly lower after CSN consumption compared to placebo (p < .05). Plasma ammonia and urea at 40th, 60th and the end of the exercise in the CSN trial were elevated compared with placebo (p < .05). Lower response in creatine kinase at 60 min during exercise and immediately after exercise was found after CSN supplementation (p < .05). Muscle glycogen content after exercise was reduced significantly in both CSN and placebo trials (p < .05). No effect was found in this study after acute oral CSN supplementation on attenuating exercise-induced fatigue, based on no significant difference responses in muscle glycogen, blood glucose and lactate. Conclusion: Oral CSN supplementation could not change lipolysis during exercise, delay muscle glycogen depletion and attenuate subsequence exercise-induced fatigue. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Efflux pump inhibitors are able to reverse antibiotic resistance by stopping efflux. • Abundant capsaicinoids are more potent than standard efflux pump inhibitors. • Synthetical capsinoids of promising antimycobacterial nature. Abstract Capsaicinoids are reported to have a bunch of promising pharmacological activities, among them antibacterial effects against various strains of bacteria. In this study the effect on efflux pumps of mycobacteria was investigated. The importance of efflux pumps, and the inhibition of these, is rising due to their involvement in antibiotic resistance development. In order to draw structure and activity relationships we tested natural and synthetical capsaicinoids as well as synthetical capsinoids. In an accumulation assay these compounds were evaluated for their ability to accumulate ethidium bromide into mycobacterial cells, a well-known substrate for efflux pumps. Capsaicin and dihydrocapsaicin, the two most abundant capsaicinoids in Capsicum species, proved to be superior efflux pump inhibitors compared to the standard verapamil. A dilution series showed dose dependency of both compounds. The compound class of less pungent capsinoids qualified for further investigation as antibacterials against Mycobacterium smegmatis. [ABSTRACT FROM AUTHOR]

Highlights • The HPLC-ESI-MS(QTOF) method has been validated for capsinoid determination. • The method developed provided higher sensitivity than the methods used routinely. • The method was used to identify capsiate and dihydrocapsiate in 8 pepper cultivars. • Capsiate was the major capsinoid in all pepper fruits. • Isomers of nornorcapsiate and nordihydrocapsiate were detected for the first time. Abstract A highly sensitive, selective method has been developed and validated for determination of capsiate and dihydrocapsiate for the first time using HPLC-ESI/MS(QTOF). For both capsinoids, LODs and LOQs were 0.02 and 0.05 µmol/l, respectively. The intra- and interday repeatability values (RSD %) were 0.26–0.41% for retention time, and 2.25–2.11% for peak area. Recoveries were up to 98% and 97% for capsiate and dihydrocapsiate, respectively. This method was successfully applied to quantify capsiate and dihydrocapsiate in eight pepper fruit accessions. Capsinoids were found in the range of 1.21–544.59 μg/g DW for capsiate and of 0.61–81.95 μg/g DW for dihydrocapsiate. In the ‘Tabasco’ accession, capsiate and dihydrocapsiate were quantified for the first time, ranging from 3.09 to 58.76 and 1.80 to 6.94 μg/g DW, respectively. Additionally, the ESI-MS/MS(QTOF) analysis has allowed the tentative identification of two other minor capsinoids by exact mass and fragmentation pattern, in the ‘Bhut Jolokia’ accession. [ABSTRACT FROM AUTHOR]

Abstract The treatment of the cotyledons of pepper plants with vanillyl nonanoate (VNT), a synthetic capsinoid similar to capsiate, protected systemically the plant against a root pathogen (the hemibiotrophic oomycete Phytophthora capsici) and an aerial pathogen (the necrotrophic fungus Botrytis cinerea). VNT treatment reduced both the symptoms and the colonization by these pathogens. VNT induced systemically two PR (Pathogenesis-related) genes and a gene involved in phytoalexin biosynthesis. VNT also induced systemically the reinforcement of cell walls with lignin both in the roots and the leaves. The increase in lignin was correlated with an increase in peroxidase gene expression and activity, pointing to the role of this enzyme in lignin polymerization. The results suggest that VNT induces systemic resistance at least in part by means of lignification. [ABSTRACT FROM AUTHOR]

Capsaicin is a widespread spice known for its analgesic qualities. Although a comprehensive body of evidence suggests pleiotropic benefits of capsaicin, including anti-inflammatory, antioxidant, anti-proliferative, metabolic, or cardioprotective effects, it is frequently avoided due to reported digestive side-effects. As the gut bacterial profile is strongly linked to diet and capsaicin displays modulatory effects on gut microbiota, a new hypothesis has recently emerged about its possible applicability against widespread pathologies, such as metabolic and inflammatory diseases. The present review explores the capsaicin–microbiota crosstalk and capsaicin effect on dysbiosis, and illustrates the intimate mechanisms that underlie its action in preventing the onset or development of pathologies like obesity, diabetes, or inflammatory bowel diseases. A possible antimicrobial property of capsaicin, mediated by the beneficial alteration of microbiota, is also discussed. However, as data are coming mostly from experimental models, caution is needed in translating these findings to humans.

Capsinoids are less pungent capsaicin analogues that increase whole body energy expenditure and hence reduce fat. Several studies have suggested that capsinoids activate brown adipose tissue (BAT), a major site of adaptive thermogenesis, but the actual contribution of BAT and uncoupling protein 1 (UCP1), a thermogenic protein expressed in BAT, to the fat-reducing effect of capsinoids has not yet been determined. Here, we investigated the effect of capsinoids on high-fat diet (HFD)-induced obesity using wild-type (WT) and UCP1-deficient (KO) mice. Capsinoids feeding potently suppressed HFD-induced increase in body weight, adiposity, and fatty liver development in WT mice. In contrast, such effects of capsinoids were completely abolished in UCP1-KO mice. Moreover, capsinoids significantly increased UCP1 protein expression in BAT without its apparent induction in white adipose tissue (WAT) in WT mice. These results indicate that capsinoids suppress diet-induced obesity of mice through the UCP1 function in BAT but not in WAT.

Interest in the consumption of the fruits of pepper (Capsicum spp.) is not only due to its organoleptic characteristics, but also due to its bioactive compounds content, which are reported to provide essential benefits to human health. However, the amount and diversity of these compounds in each fruit specimen depend on its genotype and on a number of environmental factors. This work describes the quantitative ultra-high-performance liquid chromatography coupled to photodiode-array (UHPLC-PDA) analysis of the capsinoids content in four varieties of pepper (‘Habanero’, ‘Habanero Roxo’, ‘Bode’, and ‘Malagueta’) grown until different development stages in a greenhouse under controlled conditions. In all the varieties analyzed, capsiate was the only capsinoid found. The accumulation of capsiate, in all the pepper varieties, started from the 10th to the 20th day post-anthesis (dpa), and increased during the first days (between the 20th and the 27th dpa). From that moment a drastic reduction took place until the end of the ripening stage, except for ‘Bode’ peppers, where the capsiate content increased from the first harvest point on the 20th dpa up to the 76th dpa. The capsiate accumulation patterns over the development of the fruit has been related to the capsaicionoids accumulation patterns in the same samples of the four varieties of pepper. According to our results, the content evolution of both families of compounds will vary depending on each fruit’s genotype, as well as on environmental conditions. No clear trends have been established and, therefore, an in-depth analysis under controlled conditions should be carried out.

Capsinoids are some of the most promising ingredients to increase energy expenditure (EE) due to brown adipose tissue (BAT) activation. However, there is limited information regarding the effect of prolonged capsinoid ingestion (CI) on BAT activity and resting EE (REE) in healthy, middle-aged, normal to overweight subjects (Subhealthy) with distinct BAT characteristics. We examined the changes in BAT density (BAT-d), using near-infrared time-resolved spectroscopy, and REE/kg induced by daily CI. Forty Subhealthy [age, 43.8 (mean) years; BMI, 25.4 kg/m2] received either capsinoid (9 mg/day) or a placebo daily for 6 weeks in a double-blind design. Total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, and REE/kg were measured. The changes in post-intervention [total-Hb]sup were greater in the capsinoid group (CA-G) than in the placebo group (PL-G) [5.8 µM (+12.4%) versus 1.0 µM (+2.1%); p = 0.017]. There was a significant relationship between BAT-d and REE/kg; however, post-supplementation REE/kg was not significantly different between the two groups (p = 0.228). In the overweight subgroup, changes in REE/kg were greater in the CA-G than in the PL-G [0.6 cal/kg/min (+4.3%) versus −0.3 cal/kg/min (−2.1%); p = 0.021]. CI enhanced [total-Hb]sup, a reflection of BAT-d, showing a good correlation with REE in Subhealthy.

Sedentary/inactive lifestyle leads middle-aged and older adults to metabolic syndrome and frailty. Capsinoids from nonpungent chili pepper cultivar have been reported to reduce body fat mass, promote metabolism, and improve unidentified complaints of chills. Additionally, they have an anti-inflammation effect; therefore, we hypothesized that continuous oral ingestion of capsinoids alleviates age-related inflammation in the brain and improves the physical activity (PA) in middle-aged and older adults. In our double-blind human study, 69 participants (17 male, 52 female; mean age: 74.1 ± 7.7 years; range: 52−87 years) were administered either 9 mg of capsinoids which were extracted from pepper fruit variety CH-19 Sweet (Capsicum anuum L.) (CP group), or a placebo (PL group) daily over a 3 month period. In an animal study, PA and inflammation-related mRNA expression in the brain were examined in 5-week (young) and 53-week (old) aged mice fed a diet with or without 0.3% dihydrocapsiate, a type of capsinoids, for 12 weeks. In a human study, capsinoids intake did not increase the amount of light-to-moderate PA less than 6.0 metabolic equivalents (METs) (CP: 103.0 ± 28.2 at baseline to 108.2 ± 28.3 at 12 weeks; PL: 104.6 ± 19.8 at baseline to 115.2 ± 23.6 at 12 weeks, METs × hour/week); however, in participants exhibiting an inactive lifestyle, it showed significant increase (CP: 84.5 ± 17.2 at baseline to 99.2 ± 24.9 at 12 weeks; PL: 99.7 ± 23.3 at baseline to 103.8 ± 21.9 at 12 weeks). The energy expenditure in physical activity also improved in the inactive CP group (CP: 481.2 ± 96.3 at baseline to 562.5 ± 145.5 at 12 weeks; PL: 536.8 ± 112.2 at baseline to 598.6 ± 127.6 at 12 weeks; kcal/day). In all participants, CP showed reduced waist circumference, percent body fat, and visceral fat volume; in addition, chills were eased in subjects aged 80 years and older. The older mice fed capsinoids showed increased locomotion activity, decreased inflammation, and oxidative stress in the brain. The results suggest that the continuous oral ingestion of capsinoids gains PA through anti-inflammation effect in the brain as well as reduces fat accumulation and chills in inactive and older humans.

The properties of a capsinoid, vanillyl nonanoate (VNT), to control P. capsici and B. cinerea were studied both in vitro and in vivo. In vitro tests showed that VNT inhibits the germination of P. capsici spores, but not of B. cinerea spores. The antifungal effect was caused by the whole molecule, but not by the precursor molecules corresponding to the aromatic ring and the linear chain. In vivo assays, where plants were sprayed with VNT, then inoculated, showed that the compound protected the plant from the diseases caused by P. capsici and B. cinerea. VNT induced an enhanced expression of several pepper genes related to plant defence, namely CaBGLU1, CaSC1 and CaPAL1. Because VNT had no direct toxic effect against B. cinerea, and it induced pepper defence genes, the observed protection should be due to induced resistance. [ABSTRACT FROM AUTHOR]

Background: Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We compared capsinoids and cold exposure on BAT activation and whole-body EE. Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or =2 h of cold exposure (~14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. Results: All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Conclusions: Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442. [ABSTRACT FROM AUTHOR]

Capsinoids are very similar antioxidant compounds to capsaicinoids, but less irritating, non-pungent and more palatable, and can thus be used in greater concentrations for food applications. To date, three capsinoids (capsiate, dihydrocapsiate, and nordihydrocapsiate) have been isolated from the pepper fruits. Due to its substantial commercial importance, it would be convenient to determine which pepper varieties have a richer content. Ultrasound- (UAE) and microwave- (MAE) assisted extraction have been implemented and analyzed using multivariate statistical methods. Firstly, different solvents were tested individually. The three best solvents were used in a set mixture design, where 42% methanol and 58% ethyl acetate were determined as the optimum combination for UAE, and 100% methanol for MAE. Subsequently, a Box−Behnken experimental design with four variables for both UAE and MAE (time, temperature, pH and sample mass:solvent volume “ratio”) was performed. The sample mass:solvent volume was the most influential variable in UAE; while for MAE no variable was any more influential than the others. Finally, both optimized extraction methods were successfully applied to different varieties of peppers. Besides, to demonstrate the efficiency of both extraction methods, a recovery study was performed. The results prove the potential of both techniques as highly adequate methods for the extraction of capsinoids from peppers.

Capsinoids are non-pungent analogues of capsaicinoids in pepper ( Capsicum spp). The absence of pungency, in addition to their biological activities similar to that of capsaicinoids such as anti-inflammatory, antimicrobial, and antioxidant properties, makes capsinoids an excellent option for increasing use in human and animal nutrition, as well as health and pharmaceutical industries. There are only few sources of pepper producing capsinoids, and one of them (accession 509-45-1), Capsicum annuum L., is a potential source for increasing capsinoids content using strategies as controlled elicitation during plant production in the greenhouse. In this research we evaluated the effect of weekly and one-day-before-harvest foliar applications of hydrogen peroxide, salicylic acid and a xyloglucan oligosaccharide on the concentration of capsiate in fruits of this pepper accession, as well as the gene expression of phenylalanine ammonia-lyase ( pal), putative aminotransferase ( pamt), capsaicin synthase ( at3) and β-keto acyl synthase ( kas). Results showed that the two tested concentrations of HO significantly increased capsiate content and gene expression associated with capsaicinoids ( pamt, at3 and kas) and the phenylpropanoids ( pal) pathways. Plant yield was not affected using this induction strategy. Our results indicated that the pre-harvest and weekly application of hydrogen peroxide and xyloglucan oligosaccharide improved production of capsiate in C. annuum L. [ABSTRACT FROM AUTHOR]

The ability to alter the amount and activity of brown adipose tissue (BAT) in human adults is a potential strategy to manage obesity and related metabolic disorders associated with food, drug, and environmental stimuli with BAT activating/recruiting capacity. Infrared thermography (IRT) provides a non-invasive and inexpensive alternative to the current methods (e.g. F-FDG PET) used to assess BAT. We have quantified BAT activation in the cervical-supraclavicular (C-SCV) region using IRT video imaging and a novel image computational algorithm by studying C-SCV heat production in healthy young men after cold stimulation and the ingestion of capsinoids in a prospective double-blind placebo-controlled randomized trial. Subjects were divided into low-BAT and high-BAT groups based on changes in IR emissions in the C-SCV region induced by cold. The high-BAT group showed significant increases in energy expenditure, fat oxidation, and heat output in the C-SCV region post-capsinoid ingestion compared to post-placebo ingestion, but the low-BAT group did not. Based on these results, we conclude that IRT is a promising tool for quantifying BAT activity. [ABSTRACT FROM AUTHOR]

A broad panel of Capsicum spp. landraces, mostly originating in the Andean region, was assessed with thirteen molecular markers linked to disease resistance and pungency-related traits. Tsw and L 4 were the most common loci observed within the collection, although resistant alleles associated to Pvr4 , Phyto.5.2 , and Cmr1 were also recorded in approximately 30% of pepper genotypes. South America and, namely the Andean region, revealed as a promising source of disease resistances, particularly against potyviruses . Clustering analysis split the collection into forty groups, each one carrying a distinctive combination of resistant alleles. Capsicum annuum and C. chinense showed the greatest variability, while the other Capsicum species generated homogeneous clusters with well-defined haplotypes. Capsicum chinense appeared as the most promising species for breeding purposes, with various accessions showing potential resistance to more than 80% of assessed diseases. PCoA analysis did not show a connection between those resistant genotypes and particular geographical regions. The pungency trait was predicted for 85.5% of pepper accessions. Markers linked to capsinoids content did not amplify or did not displayed polymorphism. [ABSTRACT FROM AUTHOR]

A commercial preparation of Candida rugosa lipases (CRL) was tested for the production of capsinoids by esterification of vanillyl alcohol (VA) with free fatty acids (FA) and coconut oil (CO) as acyl donors. Screening of FA chain length indicated that C8-C12 FA (the most common FA found in CO triglycerides) are the best acyl-donors, yielding 80–85% of their specific capsinoids. Hence, when CO, which is rich in these FA, was used as the substrate, a mixture of capsinoids (vanillyl caprylate, vanillyl decanoate and vanillyl laurate) was obtained. The findings presented here suggest that our experimental method can be applied for the enrichment of CO with capsinoids, thus giving it additional health promoting properties. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-positron emission tomography, in combination with computed tomography, demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT differs among individuals, being lower in older and obese individuals. Thus, BAT is recognized as a regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders. In fact, there are some food ingredients such as capsaicin and capsinoids, which have potential to activate and recruit BAT via activity on the specific receptor, transient receptor potential channels, thereby increasing energy expenditure and decreasing body fat modestly and consistently.

Capsaicin is a unique alkaloid found primarily in the fruit of the Capsicum genus and is what provides its spicy flavor. Generally extracted directly from fruit, high demand has driven the use of established methods to increase production through extraction and characterization. Over time these methods have improved, usually be applying existing techniques in conjunction. An increasingly wide range of potential applications has increased interest in capsaicin. Especially compelling are the promising results of medical studies showing possible beneficial effects in many diseases. Capsaicin’s pungency has limited its use in clinical trials to support its biological activity. Characterization and extraction/ synthesis of non-pungent analogues is in progress. A review is made of capsaicin research focusing mainly on its production, synthesis, characterization and pharmacology, including some of its main potential clinical uses in humans.

Since the recent re-discovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has attracted increasing interest. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT in association with increased energy expenditure and decreased body fatness. The stimulatory effects of cold are mediated through transient receptor potential channels (TRP), most of which are also chemesthetic receptors for various food ingredients. In fact, capsaicin and its analog capsinoids, representative agonists of TRPV1, mimic the effects of cold to decrease body fatness through the activation and recruitment of BAT. The anti-obesity effect of some other food ingredients including tea catechins may also be attributable to the activation of the TRP-BAT axis. Thus, BAT is a promising target for combating obesity and related metabolic disorders in humans. [ABSTRACT FROM AUTHOR]

Capsinoids are less pungent capsaicin analogues that increase whole body energy expenditure and hence reduce fat. Several studies have suggested that capsinoids activate brown adipose tissue (BAT), a major site of adaptive thermogenesis, but the actual contribution of BAT and uncoupling protein 1 (UCP1), a thermogenic protein expressed in BAT, to the fat-reducing effect of capsinoids has not yet been determined. Here, we investigated the effect of capsinoids on high-fat diet (HFD)-induced obesity using wild-type (WT) and UCP1-deficient (KO) mice. Capsinoids feeding potently suppressed HFD-induced increase in body weight, adiposity, and fatty liver development in WT mice. In contrast, such effects of capsinoids were completely abolished in UCP1-KO mice. Moreover, capsinoids significantly increased UCP1 protein expression in BAT without its apparent induction in white adipose tissue (WAT) in WT mice. These results indicate that capsinoids suppress diet-induced obesity of mice through the UCP1 function in BAT but not in WAT. [ABSTRACT FROM AUTHOR]