IngredientsCapsinoids are a family of naturally occurring, non-pungent phenolic compounds found in the fruit of certain Capsicum pepper cultivars. Structurally related to the well-known capsaicinoids (of which capsaicin is the principal member), capsinoids share a broad range of biological activities with their pungent counterparts while being essentially tasteless and free of the burning sensation associated with capsaicin. Their primary interest to researchers and formulators lies in their potential to stimulate energy expenditure and brown adipose tissue (BAT) thermogenesis without the oral irritation that limits the practical use of capsaicin in dietary supplements.
Capsinoids are a group of nonpungent capsaicinoid analogues produced in Capsicum fruits. The primary natural source is the low-pungent cultivar Capsicum annuum L. cv. CH-19 Sweet, a non-pungent mutant derived from a pungent pepper strain. The cultivar CH-19 Sweet is a non-pungent pepper mutant derived from a pungent pepper strain, Capsicum annuum CH-19; CH-19 Sweet biosynthesizes capsaicinoid analogues, capsinoids. CH-19 Sweet produces large amounts of capsinoids, but most pungent Capsicum lines also produce capsinoids in trace amounts.
Three mildly pungent cultivars of Capsicum chinense — Zavory Hot, Aji Dulce strain 2, and Belize Sweet — also contain high levels of capsinoids. Capsinoids occur at low concentrations in most Capsicum species. Capsiate is the major capsinoid, besides dihydrocapsiate and nordihydrocapsiate, in sweet pepper fruits, found in low concentration (0.03%) compared to capsaicinoids.
Known capsinoids include capsiate, dihydrocapsiate, and nordihydrocapsiate. Their formal chemical identifications are:
Capsinoids have been found in the range of 1.21–544.59 µg/g dry weight for capsiate and 0.61–81.95 µg/g dry weight for dihydrocapsiate across various pepper accessions.
The fundamental structure of capsinoids is a fatty acid ester with vanillyl alcohol, whereas in capsaicinoids, a fatty acid amide is linked to vanillylamine. In other words, capsaicinoids are characterized by having an amide bond, while capsinoids have an ester bond. Capsinoids are esters of vanillyl alcohol with fatty acids similar to those of capsaicinoids, while capsaicinoids are amides of vanillylamine with branched-chain fatty acids from 7 to 13 carbons in length. This single structural distinction — ester vs. amide linkage — has profound practical consequences: this structural difference is considered responsible for the lower stability of capsinoids and, therefore, for their lower pungency, assessed to be about 1,000 times lower than that of capsaicinoids.
Capsinoids are a type of fatty acid ester discovered in plants of the genus Capsicum and confirmed to be edible natural compounds. Capsinoids are less polar than capsaicinoids, due to their ester bond that replaces the amide bond of capsaicinoids. Capsinoids are considerably less chemically stable than capsaicinoids; CH-19 Sweet peppers are the source of natural capsinoids, which are less pungent and easily broken down under normal aqueous conditions, while capsaicinoids are stable in both polar and nonpolar solvents.
Capsaicin and capsiate are both synthesized from vanillin, sharing large parts of the same biosynthetic pathway. The key divergence point involves the enzyme putative aminotransferase (pAMT). pAMT is thought to catalyze the formation of vanillylamine from vanillin in the capsaicinoid biosynthetic pathway; enzyme assays revealed that pAMT activity catalyzing vanillylamine formation was completely lost in CH-19 Sweet placenta tissue. Because vanillylamine cannot be formed, vanillin is instead reduced to vanillyl alcohol, which is then esterified with fatty acids to produce capsinoids rather than the amide-linked capsaicinoids.
Previous studies on nonpungent Capsicum annuum cultivars showed that capsinoid biosynthesis is caused by loss-of-function putative aminotransferase (p-amt) alleles. In vivo experiments demonstrated that capsinoids are biosynthesized in placenta tissue of pepper fruits.
Chili peppers of the genus Capsicum have a documented history of use in food and medicine across multiple cultures, spanning centuries before the isolation of any individual constituent. In folk medicine, capsicum has been regarded as a digestive, stomachic, carminative, antispasmodic, diaphoretic, antiseptic, counterirritant, rubefacient, and tonic; internally, capsicum has been used to treat asthma, pneumonia, diarrhea, cramps, colic, toothache, and flatulent dyspepsia, and externally as a lotion or ointment to treat neuralgia, including rheumatic and arthritic pain. Capsicum is used in traditional Korean medicine; over-the-counter products are marketed for relief of oral discomfort, external analgesia, as a digestive aid, and in cosmetics. Capsicum contains approximately 1.5% irritant oleoresin, the major component of which is capsaicin (0.02%), a very pungent phenolic chemical.
In Germany, cayenne pepper is official in the German Pharmacopeia and approved in the Commission E monographs as a topical ointment for the relief of painful muscle spasms in the upper torso. In the United States, capsicum tincture and oleoresin were formerly official in the United States Pharmacopeia and National Formulary.
Capsinoids as a distinct molecular class have no independent history of traditional use. They are identified exclusively within modern scientific research. Their botanical vehicle — the CH-19 Sweet pepper — was itself developed as a selective-breeding product for research purposes, not as a culturally established food.
Capsinoids, a group of compounds analogous to capsaicinoids, were first reported in pepper fruits from the low-pungent cultivar 'CH-19 Sweet' (C. annuum) by Kobata, Todo, Yazawa, Iwai, and Watanabe in 1998. Specifically, the principal capsinoids, capsiate and dihydrocapsiate, were first isolated from the pepper (Capsicum annuum L.) cultivar CH-19 (Kobata et al., 1998). In 1999, Kobata et al. isolated a novel capsaicinoid-like substance from CH-19 Sweet and named it nordihydrocapsiate; as a group, dihydrocapsiate, capsiate, and nordihydrocapsiate are known as capsinoids. Early biochemical and physiological characterization followed rapidly in Japan during the late 1990s and early 2000s, establishing that capsinoids could replicate many of the metabolic properties of capsaicin without causing oral burning sensation.
Like capsaicin, capsinoids activate TRPV1 receptors, although they are not hot in the mouth. Capsinoids cannot reach the TRPV1 oral cavity receptors, located slightly below the surface in the mouth, because of structural differences from capsaicin. Both capsaicin and capsinoids activate TRPV1 receptors in the same manner. The thermogenic activation pathways of capsinoids include TRPV1 and TRPA1, which have possible mechanisms of action on BAT activity, because capsinoids activate both receptors.
Research has indicated that the TRPV1 receptors in the gut are important for the metabolic effects of capsaicin and capsinoids. The mechanisms by which capsinoids increase energy expenditure and fat oxidation — at least when capsinoids are orally ingested in doses below 30 mg — are likely to be explained by TRPV1 activation solely within the gastrointestinal tract.
Capsiate is known to enhance energy metabolism via activation of the sympathetic nervous system. In mice, intragastric administration of capsinoids has been shown to elicit an increase in temperature in the intrascapular BAT region, and this effect was attenuated in TRPV1-deficient animals; the thermogenic response is also impaired in humans with a mutation affecting TRPV1 function. Furthermore, capsiate is an enhancer of UCP1 expression; consequently, it is likely that capsinoids activate BAT through the TRPV1–SNS–BAT axis in humans.
Capsinoids activate transient potential receptor vanilloid 1 (TRPV1), increase sympathetic nervous system (SNS) activity and energy expenditure, and potentiate the decrease in body fat in humans. Previous studies indicate that capsinoids increase uncoupling protein 1 (UCP1) mRNA levels in BAT, UCP2 mRNA levels in epididymal fat, and UCP3 mRNA levels in skeletal muscle.
Capsinoids have an inhibitory effect on fat accumulation, which is due to increasing effects on lipid metabolism in liver and adipose tissues. In animal studies, liver — the main tissue of lipid metabolism — treated by capsinoids showed significant increases in HMG-CoA reductase, CPT-1, FAT/CD36, and GLUT4, demonstrating promotion of lipid metabolism; adding capsinoids to induced adipocytes also demonstrated significantly increased levels of these same proteins.
Capsinoids are hydrolyzed before absorption and break down to fatty acids and to vanillyl alcohol. According to human studies conducted to date, intact capsinoids are not present in the bloodstream following oral administration, suggesting minimal concern about untoward activation of TRPV1 receptors in other parts of the body. Dihydrocapsiate (DHC) is initially hydrolyzed to yield vanillyl alcohol (VOH) and 8-methyloctanoic acid; subsequently, the majority of the VOH is predominantly conjugated with glucuronic or sulfuric acid, whereas minor amounts are oxidized to vanillic acid.
The thermogenic and energy-expenditure-enhancing effects of capsinoids constitute the area of strongest and most consistent scientific investigation.
Meta-analytic evidence: A systematic review and meta-analysis was conducted to examine the effect of capsaicinoids/capsinoids on thermogenesis indices including resting metabolic rate (RMR) and respiratory quotient (RQ) in healthy adults. A literature search was conducted between 1990 and 2019 using PubMed, Web of Sciences, Scopus, the Cochrane Central Register of Controlled Trials, and EMBASE; placebo-controlled clinical trials were considered eligible. Of 4,092 articles, 13 studies were included. 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.
Key randomized controlled trial (Snitker et al., 2009): A 12-week, placebo-controlled, double-blind, randomized study investigated the safety and efficacy of capsinoids taken orally (6 mg/day) for weight loss, fat loss, and change in metabolism; eligibility criteria included a BMI of 25–35. Body weight was measured, and dual-energy X-ray absorptiometry, indirect calorimetry (men only), and genotyping were conducted. Forty women and 40 men with a mean age of 42 ± 8 years and BMI of 30.4 ± 2.4 were randomly assigned to a capsinoid or placebo group. There was no significant group difference in total change in adiposity, but abdominal adiposity decreased more (P = 0.049) in the capsinoid group (−1.11 ± 1.83%) than in the placebo group (−0.18 ± 1.94%); changes in resting energy expenditure did not differ significantly between groups, but fat oxidation was higher at the end of the study in the capsinoid group (least-squares mean difference: 21.0 mg/min; P = 0.06).
Evidence on BMI subgroups: A study monitored biochemical and physiological indices in 44 subjects after 4-week capsinoid intake; subjects were randomly assigned to three groups receiving 3 mg/kg, 10 mg/kg of capsinoids, or placebo. Measurements were performed in the morning on overnight-fasted subjects. Oxygen consumption (VO₂), resting energy expenditure (REE), and fat oxidation increased slightly compared to pre-administration values without any adverse effects, although the increase was not significant overall. The increase in fat oxidation was positively and significantly correlated with BMI, and a subsequent meta-analysis in subjects with BMI ≥ 25 (n = 28) was conducted.
Independent crossover trial (Lejeune et al., 2003): Thirteen healthy subjects received four doses of capsinoids (1, 3, 6, and 12 mg) and placebo in a crossover, randomised, double-blind trial; after a 10-hour overnight fast as inpatients, RMR was measured by indirect calorimetry for 45 minutes before and 120 minutes after ingesting capsinoids or placebo. Blood pressure and axillary temperature were also measured. At 120 minutes after dosing, metabolic rate and respiratory quotient remained similar across the four capsinoid and placebo doses. This negative result illustrates the inconsistency in the acute-dosing literature.
Evidence strength: The meta-analytic evidence supports a statistically significant increase in RMR and fat oxidation from capsaicinoids/capsinoids collectively. However, multiple individual trials show null results, heterogeneity exists across study populations, and the absolute magnitude of effect (~34 kcal/day) is modest. Evidence is strongest for the thermogenic endpoint; evidence for clinically meaningful weight loss is considerably weaker (see Section 2 below).
Systematic review and meta-analysis (body composition outcomes): A systematic review and meta-analysis was conducted to investigate the effects of capsinoids on BMI, body weight, waist circumference, waist-to-hip ratio, fat mass, fat-free mass, visceral fat area, and percentage body fat. Four databases were searched from inception to November 2020. Overall, 19 effect sizes and 13 trials with a total sample size of 838 participants were included. Capsinoids supplementation had no statistically significant effect on body weight (P = 0.230), BMI (P = 0.182), waist circumference (P = 0.611), fat mass (P = 0.946), fat-free mass (P = 0.917), waist-to-hip ratio (P = 0.599), visceral fat area (P = 0.836), or percentage body fat (P = 0.973).
Weight management review: Medical databases were searched, yielding 90 trials, 20 of which were selected for inclusion and involved 563 participants. Three main areas of potential benefit for weight management were found: (1) increased energy expenditure; (2) increased lipid oxidation; and (3) reduced appetite. It was observed that consumption of capsaicinoids increases energy expenditure by approximately 50 kcal/day.
Evidence strength: Despite consistent thermogenic signals, the most rigorous pooled analysis to date found no significant effect on direct measures of body composition including body weight, fat mass, or BMI. The energy expenditure increase, while real, appears too small and inconsistent to translate to measurable fat loss across the durations studied. Evidence for weight management is currently weak for body composition outcomes specifically, though preliminary and mixed for metabolic rate outcomes.
A single oral ingestion of capsinoids increases energy expenditure in human individuals with metabolically active BAT, but not those without it, indicating that capsinoids activate BAT and thereby increase energy expenditure; this finding gave a rational explanation for discrepant results of the effects of capsinoids in previous studies.
As human BAT may be inducible, a prolonged ingestion of capsinoids would recruit active BAT and thereby increase energy expenditure and decrease body fat.
Randomized, double-blind, placebo-controlled BAT vascular density study: A study examined changes in BAT density using near-infrared time-resolved spectroscopy, and REE/kg induced by daily capsinoid intake. Forty subjects with a mean age of 43.8 years and BMI of 25.4 kg/m² received either capsinoid (9 mg/day) or placebo capsules daily for 6 weeks in a double-blind design. The changes in post-intervention total hemoglobin concentration in the supraclavicular region — an indicator of BAT density — were greater in the capsinoid group than in the placebo group (5.8 µM [+12.4%] versus 1.0 µM [+2.1%]; p = 0.017).
Evidence strength: The BAT activation hypothesis for capsinoids is mechanistically well-supported in animal models and has some human clinical support, but human BAT-specific studies are sparse and have methodological limitations. Only one study on capsinoids analyzed BAT activity before and after the intake of dietary components, and only one study analyzed BAT activity after capsinoid ingestion; notably, the first study had a low sample size (n = 3; single-blind and crossover design). Overall, the evidence is promising but preliminary for BAT-specific outcomes in humans.
Despite their lower pungency, capsinoids exhibit similar health-promoting properties to capsaicinoids, such as being analgesic, antioxidant, anticancer, and anti-inflammatory, but without such side effects as irritation or a burning sensation. It has been reported that capsinoids induce immune responses, having anti-inflammatory and antiproliferative effects on T cells.
Evidence strength: Anti-inflammatory effects have been demonstrated largely in vitro and in animal models. Human clinical evidence specifically for capsinoids in inflammatory conditions is limited. Most clinical trial evidence for anti-inflammatory effects in the broader capsaicin/capsaicinoid literature does not isolate capsinoids specifically. This area remains at an early (preclinical) stage of evidence for capsinoids specifically.
Capsinoids have similar bioactivities to capsaicinoids, including suppression of fat accumulation and antioxidant activity. Like capsaicinoids, capsinoids possess significant antioxidant activity (Rosa et al., J. Agric. Food Chem., 50: 7396–7401, 2002). The literature has shown that compounds belonging to the capsinoids group can exhibit activities such as the restoration of gene expression of antioxidant enzymes and protection against lipid oxidation.
Evidence strength: Antioxidant activity is well-established in vitro for the capsinoid class. Dedicated human clinical trials specifically examining capsinoids as standalone antioxidant interventions are not yet available in the published literature. Evidence is primarily preclinical.
Capsinoids protect the gastric mucosa from injuries, improve glucose metabolism, and increase thermogenesis and body energy expenditure, thus becoming an effective tool for anti-obesity treatments. Capsinoids can improve glucose tolerance and have antihyperlipidemic activity, as well as anti-inflammatory and antioxidant properties.
Evidence strength: Data on glycemic control effects from capsinoids specifically (not just capsaicin) in humans are limited. The cited improvements remain largely based on animal model data or extrapolation from capsaicin studies. Human-specific capsinoid glycemic trials require further dedicated investigation.
There is no scientific consensus about the effects of capsaicinoid and capsinoid compounds on physical exercise performance and their physiological mechanisms of action; a systematic review aimed to elucidate the effects of CAP compounds as ergogenic aids. Among 22 studies included in the review, 14 examined the effects of capsaicinoid or capsinoid compounds on endurance and resistance exercise performance in animals, with 9 studies showing benefits on performance.
Null findings in resistance exercise: Twelve milligrams of dihydrocapsiate does not improve neuromuscular performance in resistance-trained young adults; dihydrocapsiate should not be recommended as an ergogenic aid to acutely increase neuromuscular performance. Even though capsinoids are not likely to affect energy expenditure and fat oxidation during low-intensity exercise activities, they could have an ergogenic role in aerobic exercises that majorly rely on glycolysis/glycogenolysis as the main source of energy, yet the evidence is scarce and uncertain.
Evidence strength: Overall evidence for capsinoids as ergogenic aids is weak and inconsistent in humans. Animal studies show more promise, but human data — particularly for resistance exercise — are predominantly null. More high-quality human trials are required before any conclusions can be drawn.
Capsinoids have an impressive list of health benefit properties, including cardiovascular effects, cited across multiple review papers. The lipid-lowering effects of capsaicin, capsinoids, and pepper-derived products have shown inconsistent results in previous research.
Evidence strength: Cardiovascular outcomes from capsinoid-specific human clinical trials are sparse. Evidence in this area is largely preliminary, derived from capsaicin or broader capsaicinoid literature, or from animal models.
Capsinoids are most commonly administered in the scientific literature as oral capsules or soft gels, either as standardized extracts from CH-19 Sweet pepper (sometimes labelled as CH-19 Sweet pepper extract) or as partially purified capsinoid preparations.
The most commonly tested maintenance dose in multi-week human trials is 6–9 mg/day, with single-dose safety studies extending to 30 mg. No formal regulatory recommended daily intake has been established for capsinoids as a supplement class by major regulatory bodies (FDA, EFSA, etc.) as of the available literature.
In the Snitker et al. 12-week capsinoid trial, none of the adverse events was considered serious and none led to withdrawal; no laboratory or electrocardiogram findings caused withdrawal. After unblinding, most treatment-emergent adverse events occurred in the placebo group; in contrast, gastrointestinal events were observed exclusively in the capsinoid group, in which four mild and diverse events were observed. Capsinoids were well tolerated.
Single-dose oral administration of up to 30 mg capsinoids did not raise blood pressure or heart rate in healthy volunteers, nor did administration of CH-19 Sweet. This contrasts with capsaicin, which has been associated with transient cardiovascular responses, and reflects the fact that intact capsinoids are not absorbed systemically.
According to human studies conducted to date, intact capsinoids are not present in the bloodstream following oral administration, suggesting minimal concern about untoward activation of TRPV1 receptors in other parts of the body; capsinoids are hydrolyzed before absorption and break down to fatty acids and to vanillyl alcohol. In the only human clinical study reported for CH-19 Sweet extract, neither capsinoids nor vanillyl alcohol was detectable in the plasma following consumption of 15 or 30 mg doses.
Capsinoids possess an ester group in place of the amide moiety; as a result of this structural change, capsinoids are not pungent and do not have the adverse side effects typically associated with capsaicin — application of capsaicin to the skin and its ingestion often result in severe irritation. Like capsaicin, capsinoids activate TRPV1 receptors, although they are not hot in the mouth; capsinoids cannot reach the TRPV1 oral cavity receptors, located slightly below the surface in the mouth, because of structural differences from capsaicin.
Of 13 genetic variants tested in the Snitker trial, TRPV1 Val585Ile and UCP2 −866 G/A correlated significantly with change in abdominal adiposity, suggesting that individual responses to capsinoids may vary based on genetic background. This has implications for both safety profiling and for interpreting the heterogeneous outcomes across clinical trials.
Capsinoids are less pungent than capsaicinoids and are easily broken down under normal aqueous conditions. This instability affects shelf life of capsinoid-containing preparations and may reduce bioactivity if products are improperly stored. Formulation as encapsulated or enteric-coated products has been explored to address this limitation, as seen in the sustained-intestinal release formulations examined in recent clinical trials.
No clinically documented drug-drug interactions specific to capsinoids (as opposed to capsaicin) were identified in the peer-reviewed literature reviewed for this article. Given that intact capsinoids are rapidly hydrolyzed in the GI tract and do not reach systemic circulation, systemic pharmacokinetic interactions are considered unlikely on theoretical grounds, though this has not been formally studied.
Health conditions that Capsinoids may help support.
Capsinoids (capsiate, dihydrocapsiate, nordihydrocapsiate) are non-pungent analogs of capsaicinoids found in sweet peppers that activate thermogenesis via TRPV1-like mechanisms. Human RCTs have documented 50–100 kcal/day increases in energy expenditure. They are recognized in the 2016 Phytotherapy Research systematic review as preferred thermogenic alternatives to capsaicin due to better tolerability.
Body systems that Capsinoids may help support.
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