Capsaicin is the molecule that is responsible for the pungency of hot peppers. It stimulates the sympathoadrenal system that mediates the thermogenic and anorexigenic effects of capsaicinoids. Capsaicinoids have been found to accentuate the impact of caloric restriction on body weight loss. Some studies have also shown that capsinoids, the non-pungent analogs of capsaicinoids, increase energy expenditure. Capsaicin supplementation attenuates or even prevents the increase in hunger and decrease in fullness as well as the decrease in energy expenditure and fat oxidation, which normally result from energy restriction. These effects may postpone the occurrence of resistance to lose fat during a weight loss program and facilitate the maintenance of body weight in a postobese state. Evidence also highlights the plausibility of an indirect effect of capsaicin on energy balance via its analgesic effects, which may improve sleep and ultimately facilitate the regulation of energy balance. Although capsaicin intake appears to be a safe practice, further studies will be needed to ascertain the safety of regular long-term consumption. Taken together, these observations reinforce the idea that consumption of capsaicinoids and capsinoids may be helpful to facilitate obesity management.
The ability to maintain an optimal functionality of mechanisms underlying body homeostasis is essential for disease prevention and preservation of personal autonomy, especially for elderly individuals. Body homeostasis can be both improved and deteriorated by numerous environmental factors, which can directly or indirectly influence some homeostatic mechanisms. In the study of obesity, the regulation of energy balance is a critical allostatic component that can be largely modified by factors such as food habits and more specifically by related nutritional and non-nutritional factors. For instance, variations in nutrient intakes can stimulate or inhibit energy intake and expenditure while other food-related constituents such as persistent organic pollutants are primarily known for their detrimental effects on energy and macronutrient balance. On the other hand, some compounds have been traditionally used in natural therapeutics to favorably influence components of energy balance and body composition. This is the case for capsaicinoids, which are considered in this paper. The main issue that is addressed is the extent to which regular consumption of capsaicinoids can facilitate the equilibrium between energy intake and expenditure in a way that prevents a positive energy balance or favors a negative energy balance in obesity-prone individuals.
Characteristics of capsaicinoids
Capsaicinoids are the pharmacologically active components of hot peppers that have been part of the diet for centuries. They constitute a family of natural products isolated from the dried fruit of chili peppers.1 The variability of their content in fresh peppers is related to the pungency of the pepper.2 The most common molecule in the capsaicinoid family is capsaicin, which is also used as the active ingredient of pepper spray. The Scoville heat value has been traditionally used as an indicator of the relative potency of hot peppers (i.e. the higher the Scoville heat value, the hotter the pepper). The Scoville heat value reminds us of the contribution of Wilbur Scoville who introduced his organoleptic test more than a century ago. This subjective test uses a panel of five trained individuals who record the hot flavor intensity of a given chili sample. The sample is diluted until pungency becomes undetectable and the dilution is expressed as the Scoville heat unit (SHU).3 Although abandoned by the food industry, the oral test of Scoville is still used in some laboratories to detect the capsaicin compound in plant extracts. Among the capsaicinoids, capsaicin and dihydrocapsaicin have the most pronounced burning effect as they are responsible for 90% of the total pungency of pepper fruit.4 Capsaicin also has analgesic properties that can contribute to the treatment of chronic pain.5 However, it also has irritant properties that may interrupt their use. Additional characteristics of capsaicinoids are shown in Table 1, which also presents a comparison with their analogs, capsinoids.
The pungency of capsaicin is frequently described as a factor that reduces its consumption and/or promotes the interruption of its use over time. This has prompted the search of analog compounds that have the potential to induce the same metabolic effects without its pungent impact. In this regard, capsinoids structurally resemble capsaicin and are reported to have similar biological activities following intravenous or oral administration to rodents and humans (Table 1). These compounds include capsiate and its analogs, dihydrocapsiate and nordihydrocapsiate, that are produced by 'CH-19 Sweet' (Capsicum annumm L.), which is a non-pungent cultivar of red peppers. Similar to capsaicinoids,6, 7 capsinoids increase plasma levels of catecholamines and sympathetic nerve activity.8, 9 Accordingly, experimental work in rats has shown that capsaicin activates mitochondrial oxygen consumption in interscapular brown adipose tissue.10 This is also in agreement with the results reported by Kawada et al.,11 suggesting that capsaicin stimulates fat mobilization from adipose tissue and reduces perirenal adipose tissue and serum triglyceride concentration in lard-fed rats. These effects are mediated by the transcient receptor potential vanilloid subtype 1, which binds with capsaicin when it is placed in the oral cavity. Both capsaicin and capsiate are passively absorbed in the stomach and the upper portion of the small intestine after binding with the high-affinity transcient receptor potential vanilloid subtype 1.12 Once released into the bloodstream, capsaicin is transported by albumin to the adrenal gland where it stimulates catecholamine release.13 Taken together, these studies demonstrate an impact of capsaicinoids and capsinoids on catecholamine levels and sympathetic activity, which are predictive of significant effects on components of energy balance.
Effects on energy expenditure
The impact of a nutrient or any other relevant active compound in the management of obesity must be mediated by significant effects on energy expenditure and/or intake. As described in this section, numerous studies have been performed to document the potential thermogenic effect of capsaicinoids. Matsumoto et al.14 observed that a capsaicin-containing yellow curry sauce increased diet-induced thermogenesis in lean but not obese young women.14 More recently, Clegg et al.15 found that in normal-weight individuals, the ingestion of a breakfast containing a combination of chili and medium-chain triglycerides increased diet-induced thermogenesis by 51% compared with a control breakfast with a pepper–sunflower oil combination.15 Ryan et al.16 evaluated the impact of a supplement combining caffeine and capsicum containing 0.67 mg of capsaicin at 100 000 SHUs on physiological responses during exercise as well as during postexercise recovery, and found that compared with a placebo, the supplement increased oxygen consumption (VO2) both during and after exercise. In the postexercise state, the increase in resting VO2 corresponded to an increase in energy expenditure of 0.3–0.4 kJ min−1 in men and women.16 The values of systolic and diastolic blood pressure as well as heart rate were also increased in men in the resting postexercise state compared with placebo. The thermogenic effect of red pepper containing capsaicin was also demonstrated immediately after a supplemented breakfast test meal compared with a breakfast control meal in men.17 Interestingly, this acute thermogenic effect was abolished by propranolol administration, which is concordant with a mediating effect of sympathetic nervous system activity.
Human studies have been performed to determine the effects of the non-pungent capsinoids on energy metabolism. In a study (n=44 overweight individuals) examining the effects of two doses (3 and 10 mg kg−1) of capsaicin analogs with low pungency in the fasting state before and after the supplementation period, it was found that the 10 mg dose increased both resting energy expenditure and fat oxidation over 4 weeks.18 In a similar study examining the impact of dihydrocapsiate consumed over 28 days on energy expenditure measured in the fasting state, Galgani and Ravussin19 found a small increase in daily resting metabolic rate after the supplement compared with a placebo (255 vs −4 kJ per day, respectively; P=0.05). These investigators also studied the effects of four doses of capsinoids (1, 3, 6 and 12 mg per day) on resting metabolic rate and the non-protein respiratory quotient in 13 healthy subjects, but found that resting metabolic rate and non-protein respiratory quotient were not modified by capsinoids. Blood pressure was also not affected by the supplementation.19 The impact of capsinoid supplementation (6 mg per day) on body weight and fat loss was also studied by Snitker et al.20 who observed an increase in lipid oxidation over 12 weeks in 80 overweight men and women. These observations indicate that both capsaicinoids and capsinoids can stimulate thermogenesis, although a higher dose might be required for capsinoids to produce this effect.
The Laval University research experience
Our clinical research has been mostly focused on the study of the acute effects of capsaicin-containing Korean red pepper on components of energy balance in humans, with a particular emphasis on variations in energy intake. In one of our first studies, Japanese women were randomly assigned to four conditions, which differed by the composition of an experimental breakfast: high-fat breakfast with or without 10 g of red pepper and high-carbohydrate meal with or without red pepper.21 Diet-induced thermogenesis was significantly greater after the high-carbohydrate meals than after the high-fat meals. The addition of red pepper to the experimental breakfast induced a significant increase in diet-induced thermogenesis and lipid oxidation, particularly after the high-fat meal. The supplementation of the high-carbohydrate breakfast with red pepper increased the perceived oiliness of the meal to the same level as that of the high-fat meals. This study also gave us the opportunity to assess the effects of capsaicin on postprandial appetite sensations and subsequent energy intake. The addition of red pepper to the high-carbohydrate breakfast significantly decreased the desire to eat and hunger before lunch.22 Moreover, the addition of red pepper to the breakfast significantly decreased protein and fat intakes at lunch time.
We pursued our study of the effects of capsaicin on energy intake by incorporating red pepper in a sauce that was part of the ingredients of an appetizer used as a food preload before subjects had free access to a buffet-type meal and subsequent snack. The addition of red pepper to the appetizer significantly decreased cumulative ad libitum energy intake by 791 kJ, which was partly explained by a significant decrease in carbohydrate intake.22 The use of power spectral analysis of heart rate revealed that the reducing effect of red pepper on energy intake was associated with an increase in the ratio of sympathetic: parasympathetic nervous system activity.
In a subsequent study, we evaluated the impact of red pepper plus caffeine supplementation on daily energy balance and its components using whole-body indirect calorimetry.23 Each participant was randomly assigned to a red pepper-caffeine or control condition. Two appetizers with or without 3 g red pepper were served before lunch and dinner during which participants could eat ad libitum. Red pepper was also included in the main course of lunch and dinner in the experimental condition. In addition, a drink (decaffeinated coffee with or without 200 mg caffeine) was provided during all meals and snacks, except for the after dinner snack. As food was consumed in a respiratory chamber, it was not surprising to observe overfeeding in each condition. As shown in Table 2, the red pepper-caffeine treatment induced a considerable decrease in daily energy intake that highlights the potential of capsaicin to prevent overfeeding. This table also indicates that the red pepper-caffeine supplementation significantly increased daily energy expenditure. However, from a quantitative standpoint, the change in energy intake was more than 11 times greater than the increase in expenditure. Overall, these modifications allowed a change in energy balance of ~4000 kJ per day. As for our preceding study, we observed a significant relationship between the decrease in energy intake and increase in the sympathetic:parasympathetic activity ratio. Subsequent research suggested that the reducing effect of red pepper on energy intake is explained by both oral and gastrointestinal exposure to capsaicin.24 In summary, these results indicate that capsaicin-containing compounds can exert a substantial effect on energy intake, which may be explained, in part, by its pungency.
The verdict of systematic reviews of literature
The study of the effects of capsaicinoids and its analogs on energy balance has been stimulated by systematic reviews of literature focusing on their effects on energy expenditure and intake as well as body weight. Recently, a review of 20 clinical trials including 563 participants investigated the effects of capsaicinoids and capsinoids on energy expenditure, lipid oxidation and appetite.25 Fifteen trials reported results on energy intake, 11 presented data on lipid oxidation and 7 documented effects on appetite. The duration of studies varied between several hours (single meal test) and 4 months (long-term intervention). The effects of capsaicinoids were examined in 12 trials, whereas eight studies tested capsinoids. The dosage of these compounds varied largely across studies ranging from 1 to 135 mg per day. Chili pepper was served as a food in 10 studies; seven trials tested the supplement, whereas both food and the supplement were used in two studies.
Most trials (13 out of 15) showed a beneficial effect of capsaicinoids or capsinoids on energy expenditure. The observed effects included an increase in metabolic rate, oxygen consumption and body temperature. The increase in energy expenditure reached about 50 kcal per day in two studies and evidence for a dose-dependent response was provided by three trials. This is in agreement with data related to lipid use since 7 out of the 11 studies that examined the effects of capsaicinoids and capsinoids on this variable revealed beneficial effects. These effects were observed in both short- and long-term studies.
Among the seven studies documenting the effects of capsaicinoids on appetite, five of them facilitated appetite control by decreasing energy intake and increasing satiety after consumption of a capsaicin-supplemented meal. In addition, a reduction in hunger and desire to eat before lunch was also observed. Three studies revealed that the decrease in appetite is independent of whether participants received oral exposure (hot sensation in the mouth) or non-oral exposure to capsaicin, although the effect was more pronounced following oral exposure. More recently, these investigators reported a systematic review and meta-analysis pertaining to the ability of capsaicinoids to contribute to the management of body weight.26 A total of eight studies involving 191 participants were included in the meta-analysis. Studies used a randomized design where participants received either a capsaicinoid intervention or placebo followed by an ad libitum test meal, with the exception of one study that used a 4-week chili supplementation in a normal diet followed by a 4-week control diet. Energy intake during the test meal was then calculated and compared between the intervention and placebo conditions. Consuming capsaicinoids resulted in a statistically significant reduction in ad libitum energy intake (310 kJ per meal). However, it is also relevant to point out that results of this meta-analysis showed high heterogeneity (I2=75.7%). To further investigate this result, Whiting et al.26 performed subgroup analyses. The variables analyzed were: ethnicity (Asian vs Caucasian), study group size (<20 vs >20 participants), intervention type (food intervention vs supplement), trial length (single meal vs multiple day), timing of the intervention (intervention given immediately before meal vs several hours before) and dosage of capsaicin (<1 vs >1 mg). Because body mass index and age of participants were similar across all trials, the authors considered them unlikely to have an impact. They found that the only significant effect was for dosage (P<0.001). Thus, they conclude that the heterogeneity could be caused by the different dosages used in the studies. However, they repeated the meta-analysis while excluding the trials with dosages <1 mg, and the heterogeneity remained high (>75%). This suggests that there might exist large variations in the trial study designs as well. Interestingly, Whiting et al.’s26 further subgroup analyses also suggested that there was a minimal effect on energy intake for dosages <2 mg (energy intake increase of 35.4 kJ or 8.4 kcal; P=0.74), whereas dosages of 2 mg or more had a significant effect (energy intake decrease of 372.0 kJ or 88.9 kcal; P<0.001). In this regard, Ahuja et al.27 reported that ingestion of more than 33 mg per day of capsaicinoids over a long period of time would not be possible because of the overpowering flavor and increase in gastric motility.
It has also been proposed that regular capsaicin consumers may become desensitized to capsaicin with effects diminishing over time. Ludy and Mattes28 observed that there was a less pronounced effect on appetite among participants who were regular capsaicin consumers before the trial. It is also relevant to point out that these authors recently reported a critical review of literature,29 indicating that both capsaicin and capsiate increase energy expenditure and fat oxidation, especially at high doses. They also emphasized that capsaicin and capsiate also have the potential to suppress orexigenic sensations.
In summary, systematic reviews of literature confirm the thermogenic and anorexigenic effects of capsaicinoids. They also demonstrate that capsinoids may lead to beneficial effects on the regulation of energy balance, although the pungency of capsaicin-containing compounds may accentuate the decrease in energy intake.
Capsaicinoids and body weight
The documented potential of capsaicinoids to influence energy intake and expenditure has favored the implementation of clinical studies in which capsaicin was incorporated into supplement formulations to facilitate body weight management. In the study of Belza et al.,30 the impact of a bioactive supplement combining capsaicin, tyrosine, catechins, caffeine and calcium was tested in the context of a diet-based weight-reducing program. As expected, the supplement increased thermogenesis and accentuated body fat loss by 0.9 kg over 8 weeks, but had no effect on blood pressure, heart rate and fecal fat loss. This is concordant with results obtained by the same research team who showed that the same supplement increased daily energy expenditure by ~200 kJ without increasing heart rate in overweight/obese individuals.31 This is also in agreement with a recent study by Lopez et al.32 who showed that a supplement containing caffeine and capsaicin accentuated body weight and fat loss during a weight loss program. These findings are also in agreement with evidence suggesting that the incidence of obesity is lower in individuals consuming capsaicinoid-containing foods.33
Finally, it is relevant to draw attention to the results of a large population study in China (n=434 556 adults) documenting the relationship between spicy food intake and anthropometric variables.34 The results showed a significant and positive association between spicy food consumption and anthropometric measures in both men and women. This observation echoes the results obtained in an animal study where old chicks demonstrated an increase in food consumption and body weight when hot red pepper was incorporated in their ad libitum diet.35 Even if the methodology of these studies does not permit the contradiction of the abundant literature reviewed above, it nevertheless emphasizes the relevance to pursue the study of variations in the response of energy balance and body weight to capsaicinoids as well as the factors that underlie these variations.
Capsaicinoids, capsinoids and obesity management
The evidence summarized above indicates that capsaicinoids and their analogs, capsinoids, fulfill the primary condition to be considered as relevant in obesity management (i.e. to promote a negative energy balance). The above-reviewed literature also shows that this can be achieved via both thermogenic stimulation and a decrease in energy intake. However, the research and clinical experience accumulated over the past few decades reveal that the ability to influence energy balance does not provide a guarantee of success in obesity management. In fact, as described in this section, the acceptability of a functional compound/ingredient in obesity management also depends on its safety and ability to favorably influence factors that contribute to the metabolic vulnerability of obesity-prone individuals.
The need for safe compounds
The ability of capsaicinoids and capsinoids to influence energy intake and expenditure via an increase in catecholamine levels and sympathetic activity raises the question of whether this might be accompanied by less desirable effects on blood pressure. This issue is important for obese individuals who might be at risk of heart-related problems. In this regard, Ahuja et al.27 reported that 4 weeks of chili supplementation resulted in a significant decrease in blood pressure and an increase in effective myocardal perfusion pressure in men. However, in another study,36 blood pressure was not modified by capsinoid supplementation in healthy men. This is in agreement with the outcome of the study of Belza et al.30 who found that treatment with a supplement containing capsaicin and caffeine had no effect on blood pressure and heart rate. On the other hand, Ryan et al.16 observed that a supplement including capsaicin and caffeine acutely increased systolic and diastolic blood pressure as well as heart rate in the postexercise state. As a result, the impact of capsaicin consumption on blood pressure and heart-related parameters appears to be unclear.
Another safety issue related to the consumption of capsaicinoids pertains to the possibility that capsaicin may be mutagenic, may favor tumor formation and act as a carcinogen.37 Of particular interest for the present paper is the possibility that hot pepper consumption increases the risk of developing stomach cancer in humans. To this effect, the population studies conducted by Notani and Jayant38 and Lopez-Carillon et al.39 confirmed the hypothesis of an increased risk of cancer in pepper consumers. However, this relationship was not observed in another population study.40
Recent evidence suggests that capsaicin has antiproliferative effects on various human cancer cell lines.41 It is believed that apoptosis, a type of programmed cell death, is the main mechanism involved in the suppression of cancer cell growth by capsaicin. Specifically, capsaicin may have anticancer activity on KB cancer cells by reducing their proliferation and viability. In another series of experiments, Min et al.42 observed that capsaicin inhibits angiogenesis.
The observations presented in this section demonstrate that the study of the safety of capsaicinoid consumption remains a clinically relevant topic of investigation. Although capsaicin can be generally considered as safe, its consumption may exert some adverse effects, especially in obese individuals who are frequently more susceptible to the development of some health-related complications. The possibility that it influences the proneness to cancers, whether positively or negatively, should also receive more attention in future clinical studies.
Improvement of cardiometabolic health
Obesity management is frequently justified by the importance of reducing the cardiometabolic risk of obese individuals with the long-term goal of preventing diabetes and cardiovascular disease. In this context, the optimal scenario occurs when a treatment modality, whether a food ingredient, drug or exercise, favors an independent improvement of metabolic fitness (i.e. that is not mediated by changes in energy balance). Ahuja et al.43 evaluated the impact of a chili meal preceded by either 4 weeks of a bland (spice-free) diet or chili diet, on plasma glucose, and serum insulin and C-peptide that was compared with the response of a bland meal preceded by a bland diet. The results showed that the maximum increase in insulin and incremental area under the curve for insulin was significantly lower after the chili meal preceded by the chili diet compared with that after the bland diet-bland meal treatment. The evidence also showed that this effect might be explained by an increase in hepatic insulin clearance. In another study, these investigators tested the effect of regular chili consumption for 4 weeks on low-density lipoprotein oxidation, which is hypothesized to be related to the development and progression of atherosclerosis.44 In a group of healthy men and women, they found that the rate of oxidation was lower after the chili diet compared with that after the bland diet. The same group used the identical design to demonstrate that the 4-week chili supplementation resulted in a significant decrease in resting blood pressure and an increase in effective myocardal perfusion pressure time in men.27 This decrease in blood pressure is interesting considering the documented impact of capsaicin on sympathetic nervous system activity.
Postprandial glycemia has been suggested to contribute to overall glycemic control. Chaiyasit et al.45 assessed the effects of Capsicum frutescens or a placebo on glycemia after an oral glucose tolerance test in 12 healthy volunteers and found that 5 g of capsicum presented capsaicin levels that were associated with a decrease in plasma glucose levels and the maintenance of insulin concentrations. Furthermore, according to the study of Ahuja et al.,43 capsicum intake also promoted a decrease in glycemia. Although the effects of capsaicin on long-term glycemic control are unclear, these studies suggest that its consumption may have implications in the management of type 2 diabetes.43
In addition to their effects on glycemia, capsaicinoids have also been suggested to have a role in endothelial health46 where capsaicin improves endothelial function and protects against lipopolysaccheride-induced apoptosis. Overall, these observations demonstrate that capsaicinoids may improve cardiometabolic health independently of their effects on energy balance and body composition.
Concomitant benefits of chronic pain reduction
Capsaicinoids are known for their analgesic properties that have been tested under conditions that are indirectly pertinent to obesity management. It has been reported that high concentrations of topical capsaicin, used to treat postherpetic neuralgia and HIV neuropathy, results in more participants experiencing a high level of pain release compared with a control treatment based on a much lower concentration of capsaicin.47 Interestingly, for individuals experiencing high levels of pain relief, additional benefits were noted for sleep, fatigue, depression and quality of life. This is concordant with research data documenting a relationship between pain and sleep quality48, 49, 50 as well as evidence showing that some treatments, for example, pregabalin, can reduce pain and improve sleep in patients with postherpetic neuralgia.51 This observation is relevant for obesity management as the improvement of sleep related to pain relief may indirectly influence energy balance and consequently the risk of overweight.52, 53 Accordingly, short sleeping was found to promote hormonal changes favoring hunger,54 to increase energy intake55 and to reduce physical activity level.56 This is also concordant with the observation that the response of body fat to caloric restriction is impaired by reduced sleep duration57, 58 and quality.57 Therefore, it is conceivable that, beyond the above-described direct effects of capsaicinoids on energy balance, they might also exert an indirect benefit via pain relief resulting in better sleep and appetite control.
Potential to decrease the physiological vulnerability induced by energy restriction: the Dutch experience
One of the most underestimated or disregarded biological contribution to obesity management is the one provided by adipose tissue, which contributes to substrate gradient effects via its release of fatty acids, to metabolic regulation via its hormonal secretion and to the prevention of metabolic antifunctionality via the storage of lipid-soluble pollutants.
The regulatory effects of adipose tissue are more palpable in response to weight loss that promotes a decrease in sympathetic nervous system activity and plasma leptin concentrations,59 which is related to a decrease in energy expenditure, in both the resting60, 61 and active62 states as well as an increase in appetite sensations.63, 64 As these effects favor body weight regain in the weight-reduced obese individuals, it is highly relevant to verify if food-related ingredients such as capsaicinoids may at least partly compensate for the impact of body fat loss on the regulation of energy balance. Over the past decade, this issue has mainly been investigated by the team of Westerterp-Plantenga and co-workers65 at the University of Maastricht. In one study, these researchers evaluated daily effects of capsaicin (39 050 SHU) on energy expenditure, substrate oxidation and blood pressure in healthy Caucasians tested in a room calorimeter, at energy balance or while subjected to a caloric deficit (75% daily energy requirements (ER)),65 under the four following conditions: 100% ER-capsaicin, 100% ER-control, 75% ER-capsaicin and 75% ER-control. The main finding of this study, relevant to this review, was that diet-induced thermogenesis and resting energy expenditure did not differ between the 75% ER-capsaicin and 100% ER-control conditions. The ability of capsaicin to counteract the reducing effect of a caloric deficit on energy metabolism was even more pronounced for fat oxidation that was greater in the 75% ER-capsaicin than in the 100% ER-control condition, whereas it did not differ between the 75% ER-control and the 100% ER-control condition. It is also worth indicating that blood pressure did not differ between conditions.
These investigators used the same design to assess the impact of these four conditions on appetite sensations.66 Their results demonstrated that satiety and fullness were higher in the 100% ER-capsaicin compared with that in the 100% ER-control condition. Capsaicin was also found to counteract the impact of an energy deficit on appetite control. Desire to eat, satiety and fullness did not differ between the 75% ER-capsaicin and 100% ER-control conditions.
This research team subsequently investigated this issue by examining the independent and combined effects of capsaicin and protein on the ability to counteract the impact of a 20% decrease in energy intake on daily energy expenditure and perceived fullness.67 For that purpose, 12 men and 12 women participated in eight randomly assigned 36-h sessions in a room calorimeter. The results showed that in comparison with the control condition with 100% ER, the 80% ER-control session induced expected effects on energy expenditure, diet-induced thermogenesis and fullness. Capsaicin consumption under the 80% ER condition counteracted these effects and accentuated the negative fat balance. The combination of capsaicin and protein in the 80% ER condition accentuated these effects. The authors concluded that capsaicin and protein, consumed alone or in combination, prevented a decrease in fullness and energy expenditure resulting from energy restriction.
This group extended their research to the study of the potential of capsaicin to attenuate the above-described vulnerability in the weight-reduced obese individual in the long-term. They tested overweight participants after they had experienced a substantial weight loss following a low-calorie diet.68 In this case, the key issue was to prevent or at least attenuate the decrease in markers of energy and fat balance that was expected to be more difficult to maintain in a weight-reduced obese state. Again, capsaicin supplementation was found to facilitate the regulation of fat balance since the participants receiving the capsaicin supplement after weight loss maintained a greater fat oxidation than control subjects. Taken together, the Dutch experience on capsaicin supplementation consistently demonstrates that capsaicin supplementation at SHU around 40 000 facilitates the control of appetite and energy expenditure when exposed to a short-term energy restriction or in the weight-reduced obese state following a longer negative energy balance. This research team has also described synergistic effects on thermogenesis that may imply capsaicinoids and caffeine or ephedrine.69 Of particular interest is the possibility that a combination of these compounds may favor long-term weight management via different mechanisms that may operate synergistically, for example, the inhibition of the phosphodiesterase-induced degradation of cAMP and the stimulation of sympathetic release of catecholamines.
The available evidence summarized in this paper supports the idea that capsaicinoid consumption may facilitate body weight management. This effect is explained by the thermogenic and appetite-reducing impact of capsaicin that is likely mediated by the stimulation of the sympathoadrenal system. When combined with other relevant compounds such as caffeine, capsaicinoids can accentuate the weight-reducing effect of an energy-restricted diet. After a substantial energy deficit that confers a vulnerable metabolic profile favoring a subsequent positive energy balance and weight regain, capsaicin supplementation was found to attenuate the increase in hunger and decrease in fullness, energy expenditure and fat oxidation. This may postpone the occurrence to further lose fat during a weight-reducing program and facilitate weight loss maintenance in a reduced obese state. Furthermore, capsaicin can attenuate overfeeding under conditions of ad libitum energy intake. Even if capsaicin consumption generally does not induce metabolic disturbances such as a significant increase in blood pressure, additional research will be useful to confirm its safety. It has also been shown that the pain relief resulting from the application of capsaicin may improve sleep, which represents an effect that may indirectly facilitate body weight management in some individuals.
Govindarajan VS, Sathyanarayana MN . Capsicum—production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences. Crit Rev Food Sci Nutr 1991; 29: 435–474.
Reilly CA, Crouch DJ, Yost GS . Quantitative analysis of capsaicinoids in fresh peppers, oleoresin capsicum and pepper spray products. J Forensic Sci 2001; 46: 502–509.
Collins MD, Wasmund LM, Bosland PW . Improved method for quantifying capsaicinoids in Capsicum using high-performance liquid chromatography. Hort Sci 1995; 30: 137–139.
Suzuki T, Kawada T, Iwai K . Biosynthesis of acyl moieties of capsaicin and its analogues from valine and leucine in capsium fruits. Plant Cell Physiol 1981; 22: 23–32.
Contri RV, Frank LA, Kaiser M, Pohlmann AR, Guterres SS . The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids. Int J Nanomed 2014; 9: 951–962.
Watanabe T, Kawada T, Iwai K . Effect of capsaicin pretreatment on capsaicin-induced catecholamine secretion from the adrenal medulla in rats. Proc Soc Exp Biol Med 1988; 187: 370–374.
Watanabe T, Kawada T, Yamamoto M, Iwai K . Capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the adrenal medulla of anesthetized rats. Biochem Biophys Res Commun 1987; 142: 259–264.
Iwai K, Yazaua A, Watanabe T . Roles as metabolic regulators of the non-nutrients, capsaicin and capsiate, supplemented to diets. Proc Jpn Acad 2003; 79: 207–212.
Shintaku K, Uchida K, Suzuki Y, Zhou Y, Fushiki T, Watanabe T et al. Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate. Br J Pharmacol 2012; 165: 1476–1486.
Yoshida T, Yoshioka K, Wakabayashi Y, Nishioka H, Kondo M . Effects of capsaicin and isothiocyanate on thermogenesis of interscapular brown adipose tissue in rats. J Nutr Sci Vitaminol (Tokyo) 1988; 34: 587–594.
Kawada T, Hagihara K, Iwai K . Effects of capsaicin on lipid metabolism in rats fed a high fat diet. J Nutr 1986; 116: 1272–1278.
Kawada T, Suzuki T, Takahashi M, Iwai K . Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. Toxicol Appl Pharmacol 1984; 72: 449–456.
Kawada T, Watanabe T, Takaishi T, Tanaka T, Iwai K . Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proc Soc Exp Biol Med 1986; 183: 250–256.
Matsumoto T, Miyawaki C, Ue H, Yuasa T, Miyatsuji A, Moritani T . Effects of capsaicin-containing yellow curry sauce on sympathetic nervous system activity and diet-induced thermogenesis in lean and obese young women. J Nutr Sci Vitaminol (Tokyo) 2000; 46: 309–315.
Clegg ME, Golsorkhi M, Henry CJ . Combined medium-chain triglyceride and chilli feeding increases diet-induced thermogenesis in normal-weight humans. Eur J Nutr 2013; 52: 1579–1585.
Ryan ED, Beck TW, Herda TJ, Smith AE, Walter AA, Stout JR et al. Acute effects of a thermogenic nutritional supplement on energy expenditure and cardiovascular function at rest, during low-intensity exercise, and recovery from exercise. J Strength Cond Res 2009; 23: 807–817.
Yoshioka M, Lim K, Kikuzato S, Kiyonaga A, Tanaka H, Shindo M et al. Effects of red-pepper diet on the energy metabolism in men. J Nutr Sci Vitaminol (Tokyo) 1995; 41: 647–656.
Inoue N, Matsunaga Y, Satoh H, Takahashi M . Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids). Biosci Biotechnol Biochem 2007; 71: 380–389.
Galgani JE, Ravussin E . Effect of dihydrocapsiate on resting metabolic rate in humans. Am J Clin Nutr 2010; 92: 1089–1093.
Snitker S, Fujishima Y, Shen H, Ott S, Pi-Sunyer X, Furuhata Y et al. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. Am J Clin Nutr 2009; 89: 45–50.
Yoshioka M, St-Pierre S, Suzuki M, Tremblay A . Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanese women. Br J Nutr 1998; 80: 503–510.
Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M et al. Effects of red pepper on appetite and energy intake. Br J Nutr 1999; 82: 115–123.
Yoshioka M, Doucet E, Drapeau V, Dionne I, Tremblay A . Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods. Br J Nutr 2001; 85: 203–211.
Westerterp-Plantenga MS, Smeets A, Lejeune MP . Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int J Obes (Lond) 2005; 29: 682–688.
Whiting S, Derbyshire E, Tiwari BK . Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of the evidence. Appetite 2012; 59: 341–348.
Whiting S, Derbyshire EJ, Tiwari B . Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data. Appetite 2014; 73: 183–188.
Ahuja KD, Robertson IK, Geraghty DP, Ball MJ . The effect of 4-week chilli supplementation on metabolic and arterial function in humans. Eur J Clin Nutr 2007; 61: 326–333.
Ludy MJ, Mattes RD . The effects of hedonically acceptable red pepper doses on thermogenesis and appetite. Physiol Behav 2011; 102: 251–258.
Ludy MJ, Moore GE, Mattes RD . The effects of capsaicin and capsiate on energy balance: critical review and meta-analyses of studies in humans. Chem Senses 2012; 37: 103–121.
Belza A, Frandsen E, Kondrup J . Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond) 2007; 31: 121–130.
Belza A, Jessen AB . Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. Eur J Clin Nutr 2005; 59: 733–741.
Lopez HL, Ziegenfuss TN, Hofheins JE, Habowski SM, Arent SM, Weir JP et al. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women. J Int Soc Sports Nutr 2013; 10: 22.
Wahlqvist ML, Wattanapenpaiboon N . Hot foods—unexpected help with energy balance? Lancet 2001; 358: 348–349.
Sun D, Lv J, Chen W, Li S, Guo Y, Bian Z et al. Spicy food consumption is associated with adiposity measures among half a million Chinese people: the China Kadoorie Biobank study. BMC Public Health 2014; 14: 1293.
Al-Kassie GAM, Al-Nasrawi MAM, Ajeena SJ . The effects of using hot red pepper as a diet supplement on some performance traits in broiler. Pak J Nutr 2011; 10: 842–845.
Galgani JE, Ryan DH, Ravussin E . Effect of capsinoids on energy metabolism in human subjects. Br J Nutr 2010; 103: 38–42.
Szallasi A, Blumberg PM . Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 1999; 51: 159–212.
Notani PN, Jayant K . Role of diet in upper aerodigestive tract cancers. Nutr Cancer 1987; 10: 103–113.
Lopez-Carrillo L, Hernandez Avila M, Dubrow R . Chili pepper consumption and gastric cancer in Mexico: a case–control study. Am J Epidemiol 1994; 139: 263–271.
Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S et al. A case–control study of gastric cancer and diet in Italy. Int J Cancer 1989; 44: 611–616.
Lin CH, Lu WC, Wang CW, Chan YC, Chen MK . Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Altern Med 2013; 13: 46.
Min JK, Han KY, Kim EC, Kim YM, Lee SW, Kim OH et al. Capsaicin inhibits in vitro and in vivo angiogenesis. Cancer Res 2004; 64: 644–651.
Ahuja KD, Robertson IK, Geraghty DP, Ball MJ . Effects of chili consumption on postprandial glucose, insulin, and energy metabolism. Am J Clin Nutr 2006; 84: 63–69.
Ahuja KD, Ball MJ . Effects of daily ingestion of chilli on serum lipoprotein oxidation in adult men and women. Br J Nutr 2006; 96: 239–242.
Chaiyasit K, Khovidhunkit W, Wittayalertpanya S . Pharmacokinetic and the effect of capsaicin in Capsicum frutescens on decreasing plasma glucose level. J Med Assoc Thai 2009; 92: 108–113.
Chularojmontri L, Suwatronnakorn M, Wattanapitayakul SK . Influence of capsicum extract and capsaicin on endothelial health. J Med Assoc Thai 2010; 93 (Suppl 2): S92–101.
Derry S, Sven-Rice A, Cole P, Tan T, Moore RA . Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2013; 2: CD007393.
Morin CM, Gibson D, Wade J . Self-reported sleep and mood disturbance in chronic pain patients. Clin J Pain 1998; 14: 311–314.
Raymond I, Nielsen TA, Lavigne G, Manzini C, Choiniere M . Quality of sleep and its daily relationship to pain intensity in hospitalized adult burn patients. Pain 2001; 92: 381–388.
Sayar K, Arikan M, Yontem T . Sleep quality in chronic pain patients. Can J Psychiatry 2002; 47: 844–848.
Sabatowski R, Galvez R, Cherry DA, Jacquot F, Vincent E, Maisonobe P et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004; 109: 26–35.
Chaput JP, Brunet M, Tremblay A . Relationship between short sleeping hours and childhood overweight/obesity: results from the 'Quebec en Forme' Project. Int J Obes (Lond) 2006; 30: 1080–1085.
Boule NG, Chaput JP, Doucet E, Richard D, Despres JP, Bouchard C et al. Glucose homeostasis predicts weight gain: prospective and clinical evidence. Diabetes Metab Res Rev 2008; 24: 123–129.
Spiegel K, Tasali E, Penev P, Van Cauter E . Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med 2004; 141: 846–850.
Brondel L, Romer MA, Nougues PM, Touyarou P, Davenne D . Acute partial sleep deprivation increases food intake in healthy men. Am J Clin Nutr 2010; 91: 1550–1559.
Schmid SM, Hallschmid M, Jauch-Chara K, Wilms B, Benedict C, Lehnert H et al. Short-term sleep loss decreases physical activity under free-living conditions but does not increase food intake under time-deprived laboratory conditions in healthy men. Am J Clin Nutr 2009; 90: 1476–1482.
Chaput JP, Tremblay A . Sleeping habits predict the magnitude of fat loss in adults exposed to moderate caloric restriction. Obes Facts 2012; 5: 561–566.
Nedeltcheva AV, Kilkus JM, Imperial J, Schoeller DA, Penev PD . Insufficient sleep undermines dietary efforts to reduce adiposity. Ann Intern Med 2010; 153: 435–441.
Rosenbaum M, Kissileff HR, Mayer LE, Hirsch J, Leibel RL . Energy intake in weight-reduced humans. Brain Res 2010; 1350: 95–102.
Doucet E, St-Pierre S, Almeras N, Despres JP, Bouchard C, Tremblay A . Evidence for the existence of adaptive thermogenesis during weight loss. Br J Nutr 2001; 85: 715–723.
Leibel RL, Rosenbaum M, Hirsch J . Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995; 332: 621–628.
Doucet E, Imbeault P, St-Pierre S, Almeras N, Mauriege P, Despres JP et al. Greater than predicted decrease in energy expenditure during exercise after body weight loss in obese men. Clin Sci (Lond) 2003; 105: 89–95.
Doucet E, Imbeault P, St-Pierre S, Almeras N, Mauriege P, Richard D et al. Appetite after weight loss by energy restriction and a low-fat diet-exercise follow-up. Int J Obes Relat Metab Disord 2000; 24: 906–914.
Doucet E, St-Pierre S, Almeras N, Tremblay A . Relation between appetite ratings before and after a standard meal and estimates of daily energy intake in obese and reduced obese individuals. Appetite 2003; 40: 137–143.
Janssens PL, Hursel R, Martens EA, Westerterp-Plantenga MS . Acute effects of capsaicin on energy expenditure and fat oxidation in negative energy balance. PLoS One 2013; 8: e67786.
Janssens PL, Hursel R, Westerterp-Plantenga MS . Capsaicin increases sensation of fullness in energy balance, and decreases desire to eat after dinner in negative energy balance. Appetite 2014; 77: 44–49.
Smeets AJ, Janssens PL, Westerterp-Plantenga MS . Addition of capsaicin and exchange of carbohydrate with protein counteract energy intake restriction effects on fullness and energy expenditure. J Nutr 2013; 143: 442–447.
Lejeune MP, Kovacs EM, Westerterp-Plantenga MS . Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr 2003; 90: 651–659.
Diepvens K, Westerterp KR, Westerterp-Plantenga MS . Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol 2007; 292: R77–R85.
SP is the recipient of a postdoctoral fellowship from the Canadian Diabetes Association. AT is partly funded by the Canada Research Chair in Environment and Energy Balance.
AT is sponsored by OmniActive Health Technologies. The remaining authors declare no conflict of interest.
About this article
Cite this article
Tremblay, A., Arguin, H. & Panahi, S. Capsaicinoids: a spicy solution to the management of obesity?. Int J Obes 40, 1198–1204 (2016). https://doi.org/10.1038/ijo.2015.253
The Beneficial Effects of Red Sun‐Dried Capsicum annuum L. Cv Senise Extract with Antioxidant Properties in Experimental Obesity are Associated with Modulation of the Intestinal Microbiota
Molecular Nutrition & Food Research (2021)
Factors affecting the capsaicinoid profile of hot peppers and biological activity of their non-pungent analogs (Capsinoids) present in sweet peppers
Critical Reviews in Food Science and Nutrition (2021)
Critical Reviews in Food Science and Nutrition (2020)
Brown Adipose Tissue, Diet-Induced Thermogenesis, and Thermogenic Food Ingredients: From Mice to Men
Frontiers in Endocrinology (2020)
Challenging energy balance - during sensitivity to food reward and modulatory factors implying a risk for overweight - during body weight management including dietary restraint and medium-high protein diets
Physiology & Behavior (2020)