Dietary capsaicin and its anti-obesity potency: From
mechanism to clinical implications
Jia Zheng1, Sheng Zheng2, Qianyun Feng2, Qian Zhang1, Xinhua Xiao1*
1Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health,
Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy
of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
2Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
*Corresponding author: Xinhua Xiao, E-mail: firstname.lastname@example.org; Tel:
+86-10-69155073. No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing
100730, P. R. China.
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Abstract: Obesity is a growing public health problem, which has now been considered as
a pandemic non-communicable disease. However, the efficacy of several approaches for
weight loss is limited and variable. Thus, alternative anti-obesity treatments are urgently
warranted, which should be effective, safe and widely available. Active compounds
isolated from herbs are similar with the practice of Traditional Chinese Medicine, which
has a holistic approach that can targets to several organs and tissues in the whole body.
Capsaicin, a major active compound from chili peppers, has been clearly demonstrated
for its numerous beneficial roles in health. In this review, we will focus on the a less
highlighted aspect, in particular how dietary chili peppers and capsaicin consumption
reduce body weight and its potential mechanisms of its anti-obesity effects. With the
widespread pandemic of overweight and obesity, the development of more strategies for
the treatment of obesity is urgent. Therefore, a better understanding of the role and
mechanism of dietary capsaicin consumption and metabolic health can provide critical
implications for the early prevention and treatment of obesity.
Keywords: Capsaicin; obesity; TRPV1; adipogenesis; brown adipose tissue; appetite
Abbreviations (alphabetically): BAT, brown adipose tissue; BMI, body mass index;
BMP8b, bone morphogenetic protein-8b; cAMP, cyclic adenosine monophosphate;
C/EBP-Į, CCAAT-enhancer-binding protein-Į; PKA, protein kinase A; GLP-1,
glucagon-like peptide-1; GPDH, glycerol-3-phosphate dehydrogenase; Muc2, mucin 2
gene; NF-țB, nuclear factor- kappa B; PPARĮ, peroxisome proliferator activated
receptor Į; PPARȖ, peroxisome proliferator activated receptor-Ȗ; PRDM-16, positive
regulatory domain containing 16; PGC1-Į, PPARȖ coactivator 1-Į; Reg3g, regenerating
islet-derived protein 3 gamma; SIRT-1, sirtuin-1; STAT-3, signal transducer and
activator of transcription-3; T2DM: type 2 diabetes mellitus; TRPV1, transient receptor
potential vanilloid 1; UCP-1, uncoupling protein 1; WAT, white adipose tissue˗WHO˖
World Health Organization.
The epidemic of obesity is a growing public health problem. The incidence of obesity has
more than doubled since 1980, and has now reached worldwide epidemic status . In
2014, the World Health Organization (WHO) estimated that 39% of the human adult
population with 1.9 billion people were affected with overweight (body mass index (BMI)
ı25 kg/m2), and that obesity (BMIı30 kg/m2) affected about 13% with 600 million
people [2, 3]. Obesity is a serious risk factor as it is associated with chronic inflammation
and metabolic syndrome , a cluster of morbidities that includes hypertension,
hyperlipidemia and type 2 diabetes mellitus (T2DM) . It can increase the risks of
developing serious health problems, such as cardiovascular diseases, chronic kidney
disease and stroke [6, 7]. Moreover, obese patients are more prone to contract several
forms of cancer with reduced chances of survival . Of particular concern is the
incidence of overweight and obesity in children, with an estimated one-third of children
and adolescents affected in the United States and over 41 million children are overweight
before reaching puberty . As such, obesity and its related diseases yield enormous tolls
at individual, public health and economic levels. In addition, genome-wide association
studies (GWAS) have revealed compelling genetic signals influencing obesity risk and
genetic polymorphism plays a major role in determining obesity . An updated
randomized controlled trial indicated that greater body weight and waist circumference
reductions in risk carriers than in nonrisk carriers of the fat-mass and obesity-associated
(FTO) geneacross different levels of personalized nutrition . These data signify that
the interventions should be personalized and varies with each individual . Thus, the
development of novel and personalized strategies for the early prevention and treatment
of overweight and obesity is warrant.
2. Limitations in anti-obesity approaches
It has clearly established that weight loss will significantly diminish the complications of
obesity . Emerging human epidemiology studies indicated that reducing body weight,
with weight loss of at least 5%, has long-term benefits on metabolic health and reduces
the risks of developing insulin resistance, T2DM and cardiovascular diseases .
However, weight loss is difficult and the obese individuals are struggling to achieve it
and the efficacy of several approaches for weight loss is limited and variable [14, 15].
Firstly, it is widely accepted that a combination of physical exercise and low calorie diet
is the best approach to prevent and treat obesity. However, this strategy is difficult to
implement and its compliance is poor. Gupta et al. aimed to explored treatment
satisfaction associated with different weight loss methods among patients with obesity. It
showed that using self-modification weight loss techniques, such as, diet, exercise and
weight loss supplements has lowest treatment satisfaction, compared with gastric bypass
and gastric banding, and prescription medication . In addition, physical exercise and
diet intervention also yield enormous tolls at economic level. It reported that retail sales
of weight-loss supplements were estimated to be more than $1.3 billion in 2001 in US
. Thus, cheap, easily available therapies and supplements are urgently needed. The
second approach is pharmaceutical drugs, such as Orlistat, a potent and specific inhibitor
of intestinal lipases. It can reduce body weight with an average weight loss of 3% during
one year period . However, its efficacy is variable and it can lead to gastrointestinal
adverse effects, liver failure and acute kidney injury . Other anti-obesity drugs, such
as rimonabant, fenfluraminea and sibutramine, have been withdrawn from the market due
to severe adverse effects, including increased cardiovascular risks, mood disorders and
even suicidal susceptibility . Thirdly, anti-diabetic agents, such as, glucagon-like
peptide 1 (GLP-1) analogue, liraglutide has been shown its potential anti-obesity efficacy
. But it needs to be injected subcutaneously daily. Moreover, the weight loss is
limited and it can increase the risk of pancreatitis . Compared with aforementioned
anti-obesity drugs, bariatric surgery such as Roux-en-Y gastric bypass or sleeve
gastrectomy is more effective. However, it is physically invasive, relatively expensive
and its long-term effect is unclear . Therefore, alternative anti-obesity treatments are
urgently warranted, which should be effective, safe and widely available.
3. An overview of chili peppers and capsaicin
Chili pepper is generally used as a flavoring spice and is prominent in diets of various
communities and cultures worldwide since 7000BC, with a long history of flavoring,
coloring, preserving food as well as medication . In chili pepper, more than 200
active constituents have been identified and some of its active constituents play multiple
roles in the whole body . Capsaicin, as a major active compound from chili pepper,
has been established for its numerous beneficial roles in the human organism, including
the treatment of pain inflammation, rheumatoid arthritis  and vasomotor rhinitis 
(Figure 1). Furthermore, capsaicin has proven an effective anti-cancer agent. Several
preclinical studies showed that capsaicin could suppress various human neoplasia by
generating reactive oxygen species and increasing apoptosis [30, 31]. Finally, capsaicin
demonstrated significant antioxidant properties and it was postulated that this compound
has important implications in the prevention or treatment of neurodegenerative diseases
such as Alzheimer’s disease . In addition tocapsaicin as anti-obesity compounds,
other types of natural products also have shown to be considered as anti-obesity
compounds. Celastrol (from roots of the thunder god vine) can reduce appetite and food
intake in mice that are fed a high-fat diet . Stilbenoid resveratrol (from grapes and red
wine), genistein (an isoflavone from soy), glycyrrhizin (from liquorice), quercetin,
ethanolic extract (from ginseng roots) and green tea extract (including camellia sinensis,
catechin, caffeine, and epigallocatechin gallate), play a role in adipogenesis inhibition,
thus may have anti-obesity potency . In this review, we will focuses on the a less
highlighted aspect, in particular how dietary chili peppers and capsaicin consumption
reduce body weight and its potential mechanisms of its anti-obesity effects. Figure 1
shows the molecular structure of capsaicin and isolated from chili peppers.
4. Clinical studies of the weight-loss effects of capsaicin
4.1 Weight-loss effects of capsaicin on lipid oxidation and energy expenditure
Epidemiological data revealed that the consumption of foods containing capsaicin was
associated with a lower prevalence of obesity . In one double-blind, randomized,
placebo controlled trial, it indicated that treatment of overweight or obese subjects with 6
mg/d capsinoid for 12 weeks was associated with abdominal fat loss measured by dual
energy X-ray absorptiometry. Body weight was decreased as 0.9 and 0.5 kg in the
capsinoid and placebo groups, respectively. Moreover, none of the patients developed any
adverse events  (Table 1). Lejeune et al. aimed to investigate whether capsaicin
assists weight maintenance by limiting weight regain after weight loss of 5% to 10%. The
results showed that capsaicin treatment caused sustained fat oxidation during weight
maintenance compared with placebo  (Table 1). Increase the oxygen consumption
(VO2) and body temperature, reflecting increased energy expenditure, thus play critical
role in weight loss. Fat oxidation was reported to be sustained together with elevation of
the resting energy expenditure and enhanced fat oxidation may contribute to increased
energy expenditure. In another randomized double-blind study, it indicated that subjects
between 30 and 65-year old with a BMI >23 kg/m2 treated with capsinoid (10 mg/kg per
day) for 4 weeks safely and body weight tended to decrease during the 2 to 4 week period,
with increased VO2, resting energy expenditure, fat oxidation significantly  (Table 1).
Enhanced lipid oxidation and increased energy expenditure are potentially beneficial for
weight management .
4.2 Weight-loss effects of capsaicin on appetite and brown adipose tissue
Dietary red pepper can suppress energy intake and modify macronutrient intake through
appetite and satiety regulation . One prospective study aimed to investigate the
effects of capsaicin on feeding behavior and energy intake. It indicated that the addition
of red pepper to the breakfast significantly decreased protein and fat intakes at lunch time
and the addition of red pepper to the appetizer significantly reduced the cumulative ad
libitum energy and carbohydrate intakes during the rest of the lunch. These effects might
be related to an increase in sympathetic nervous system activity  (Table 1). Brown
adipose tissue (BAT) is known to play a critical role in cold-induced non-shivering
thermogenesis to maintain body temperature and it is expected to be a therapeutic target
for obesity and related metabolic disorders in humans . It showed Chili pepper affects
energy expenditure by triggering the BAT in the same way as low temperature does,
leading to increased energy expenditure via non-shivering thermogenesis . One recent
clinical study showed that 9 mg of capsinoid for 8 weeks could increase BAT activity and
increase thermogenesis in healthy subjects  (Table 1). The results suggest dietary
capsaicin consumption could have a beneficial effect for weight management, by
reducing energy intake and activation of brown adipose tissue activity. The summary of
the clinical studies about the weight-loss effects of capsaicin was shown Table 1.
5. Pre-clinical studies aboutanti-obesity effects of capsaicin and its potential
5.1 Capsaicin and TRPV1 activation
Numerous epidemiology studies and animal studies indicated that capsaicin, as a transient
receptor potential vanilloid 1 (TRPV1) agonist, it may represent a potential strategy to
treat obesity. Although it is well accepted much of the effect is caused by stimulation of
the TRPV1 receptor, the mechanism of action is not presently fully understood.
Increasing evidence indicates that TRPV1 plays a critical role in the regulation of
metabolic health for the whole body, including body weight, glucose and lipid
metabolism, and cardiovascular system [44, 45]. TRPV1 was deemed as a potential target
for the prevention of obesity due to its effect on energy metabolism and balance [46, 47].
Activation of TRPV1 by capsaicin can attenuate abnormal glucose homeostasis by
stimulating insulin secretion and increasing glucagon-like peptide-1 (GLP-1) levels [48,
49] (Table 2). Furthermore, capsaicin also plays its role in a receptor-independent manner.
It reported that capsaicin was associated with nuclear factor-kappa B (NF-țB)
inactivation and peroxisome proliferator activated receptor-Ȗ (PPARȖ) activation, and
then it could modulate adipocyte function of adipose tissues in obese-mouse and
suppressed the inflammatory responses of adipose tissue macrophages, which is
independent on TRPV1 . Additionally, TRPV1 can play a critical role in cell
proliferation and cancer. It showed that TRPV1 implicated as a regulator of growth factor
signaling in the intestinal epithelium, which could subsequent suppress intestinal
The potential mechanisms underlying the anti-obesity effects of capsaicin include: (1)
increase lipid oxidation and inhibit adipogenesis; (2) activate brown adipose tissue (BAT)
activity and induce thermogenesis; (3)suppress appetite and increase satiety regulated by
neuronal circuits in the hypothalamus; (4) modulate the function of gastrointestinal tract
and gut microbiome. The molecular mechanisms of the anti-obesity effects of capsaicin
were summarized in Figure 2. In addition, we further collected most pre-clinical studies,
including in-vitro studies and rodent experiments about the anti-obesity effects of
capsaicin (shown in Table 2).
5.2 Capsaicin and its role in adipogenesis
Adipogenesis is the critical and original process of fatty adipose accumulation. It
suggested that decreased preadipocyte differentiation, proliferation and lipogenesis have
the potential to reduce obesity. Hsu et al. demonstrated that capsaicin inhibited the
expression of PPARȖ, CCAAT-enhancer-binding protein-Į (C/EBP-Į) and leptin, but
induced up-regulation of adiponectin at the protein level. Thus, it efficiently induced
apoptosis and inhibits adipogenesis in 3T3-L1 preadipocytes and adipocytes in vitro 
(Table 2, Figure 2). Zhang et al. found that capsaicin treatment prevented adipogenesis of
3T3-L1-preadipocytes in vitro, with increased intracellular calcium  (Figure 2). Male
C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015%
capsaicin showed decreased fasting glucose, insulin, leptin concentrations, and markedly
improved glucose intolerance in obese mice, accompanied with decreased TRPV-1
expression in adipose tissue, increased adiponectin expression in the adipose tissue and
increased peroxisome proliferator activated receptor Į (PPARĮ) and PPARȖ coactivator
1-Į (PGC-1Į) expression in the liver  (Table 2, Figure 2). Ohnuki et al. demonstrated
that mice treated with 10 mg/kg body weight capsaicin could markedly suppressed body
fat accumulation and promoted energy metabolism  (Table 2). Hence, these studies
supported that capsaicin could decrease adipogenensis and regulate genes function related
with lipid metabolism, and then it can has the potential to lose weight.
5.3 Capsaicin and its role in brown adipose tissue
BAT is the main site of adaptive thermogenesis and experimental studies have associated
BAT activity with protection against obesity and metabolic diseases . A review
illustrated that the activity of BAT can be activated and recruited not only by cold
exposure but also by various food ingredients, such as capsaicin in chili pepper 
(Table 2). Capsinoids supplementation with exercise in C57BL/6J mice additively
decreased body weight gain and fat accumulation, and increased whole body energy
expenditure compared with exercise alone. The underlying mechanisms may be
associated with increased energy expenditure, lipolysis activation in BAT and increased
cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity in
BAT  (Table 2, Figure 2). One up-to-date rodent experiment showed that capsaicin
could counter the detrimental effects of high-fat diet, including glucose intolerance,
hypercholesterolemia and suppressed activity in BAT. These effects were mainly by
increasing the expression of metabolically important thermogenic genes, including
uncoupling protein 1 (UCP-1), bone morphogenetic protein-8b (BMP8b), sirtuin-1
(SIRT-1), PGC-1Į and PR domain containing zinc finger protein 16 (PRDM-16) in BAT.
Furthermore, capsaicin supplementation, post high-fat diet, promoted weight loss and
enhanced the respiratory exchange ratio. All these data suggested that capsaicin is a novel
strategy to counter diet-induced obesity by enhancing metabolism and energy expenditure
 (Table 2, Figure 2). Baskaran et al. showed that activation of TRPV1 channels by
dietary capsaicin triggered browning of adipose tissue to counteract obesity  (Table 2).
Collectively, these observations provide evidence that capsaicin can activate and recruit
BAT, which would be a promising strategy to counter obesity.
5.4 Capsaicin and its role in appetite and satiety
Energy balance requires an ability of the brain to detect the status of energy stores and
match energy intake with expenditure, and energy homeostasis is mainly controlled by
neuronal circuits in the hypothalamus . Hypothalamic endoplasmic reticulum stress
occurs in individuals with obesity and is thought to induce low levels of leptin receptor
signaling and play a central role in development of leptin resistance . The adipose
tissue-derived hormone leptin acts via its receptor in the brain to regulate energy balance
and neuroendocrine function. Leptin resistance is a pathological condition, which means
the lack of appetite reduction in response to leptin and the body fails to adequately
respond to it . Lee et al. found that TRPV1 had a major role in regulating glucose
metabolism and hypothalamic leptin's effects in obesity, with hypothalamic signal
transducer and activator of transcription-3 (STAT-3) activity blunted in the TRPV1 knock
out mice  (Figure 2). Addition of dietary capsaicin has been shown to increase satiety
and it indicated that capsaicin increased sensation of fullness in energy balance, and
decreased desire to eat after dinner in negative energy balance . Although the studies
about capsaicin and its role in appetite is limited, it inspired us that neuronal circuits in
the hypothalamus may be a pivotal target of capsaicin.
5.5 Capsaicin and its role in gastrointestinal tract and gut microbiome
Capsaicin is passively absorbed in the stomach with greater than 80% efficiency and
upper portion of the small intestine . Thus, it may activate local TRPV1 channels in
gastrointestinal tract to initiate a series of physiological effects. Dietary capsaicin
consumption triggered the intestinal mucosal afferent nerves and increased intestinal
blood flow . Acute single administration of 640 umol/L capsaicin into the duodenal
lumen in anesthetized rats significantly increases superior mesenteric artery blood flow
 (Table 2). In addition, it showed that dietary capsaicin ameliorated abnormal glucose
homeostasis and increased GLP-1 levels in the plasma and ileum through the activation
of TRPV1-mediated GLP-1 secretion in the intestinal cells and tissues  (Table 2,
Figure 2). Recent study demonstrated that anti-obesity effect of capsaicin in mice fed
with high-fat diet was associated with an increase in population of the gut bacterium
Akkermansia muciniphila. Further studies found that capsaicin directly up-regulated the
expression of Mucin 2 gene Muc2 and antimicrobial protein gene regenerating
islet-derived protein 3 gamma (Reg3g) in the intestine (Table 2, Figure 2). These data
suggested that the anti-obesity effect of capsaicin is associated with a modest modulation
of the function in gastrointestinal tract and gut microbiome.
In summary, capsaicin plays a critical role in human and has multiple benefits for
metabolic health, especially for weight loss in obese individuals. It is well accepted that
the potential application of active compounds isolated from herbs are similar with the
practice of traditional Chinese medicine, which has a holistic approach that can targets to
different organs and tissues in the whole body. More importantly, no adverse effects with
capsaicin were observed in most studies. Thus, chili peppers and capsaicin are safely and
easily applicable to our daily life. Considering that chili peppers have been a vital part of
culinary cultures worldwide and have a long history of use for flavoring, so it is more
feasible to be utilized to treat overweight and obesity, compare with medications or other
interventionswith certain side effects. Dietary chili peppers supplementation or to be
food additives, with ideal dosage may be tentative methods for capsaicin to play its
protective roles in metabolic health. With the widespread pandemic of overweight and
obesity, the development of more strategies for the treatment of obesity is urgent.
Therefore, a better understanding of the role and mechanism of dietary capsaicin
consumption and metabolic health can provide critical implications for the early
prevention and treatment of obesity.
Competing Interest: The authors declare that there are no competing interests associated
with the manuscript.
Acknowledgments: This work was supported by the National Natural Science
Foundation of China (No. 81170736, 81570715), National Key Research and
Development Program of China (No. 2016YFA0101002) and National Natural Science
Foundation for Young Scholars of China (No. 81300649) and China Scholarship Council
Foundation (No. 201506210378). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
Author Contribution: J.Z. and X.H.X. have made substantial contributions to ideas,
conception and design of the review. S.Z. and Q.Y.F. searched the databases, selected
studies, extracted the data and wrote the manuscript. S.Z. and Q.Z. reviewed and edited
the manuscript. X.H.X. contributed to the design and reviewed and edited the manuscript.
1. Caballero, B., The global epidemic of obesity: an overview. Epidemiol Rev, 2007.
29: p. 1-5.
2. Organization, W.H., Obesity and overweight. 2016.
3. Ogden, C.L., et al., Prevalence of childhood and adult obesity in the United States,
2011-2012. Jama, 2014. 311(8): p. 806-14.
4. Canale, M.P., et al., Obesity-related metabolic syndrome: mechanisms of
sympathetic overactivity. Int J Endocrinol, 2013. 2013: p. 865965.
5. Khodabandehloo, H., et al., Molecular and cellular mechanisms linking
inflammation to insulin resistance and beta-cell dysfunction. Transl Res, 2016.
167(1): p. 228-56.
6. Kotsis, V., et al., New developments in the pathogenesis of obesity-induced
hypertension. J Hypertens, 2015. 33(8): p. 1499-508.
7. Mascali, A., et al., Obesity and kidney disease: Beyond the hyperfiltration. Int J
Immunopathol Pharmacol, 2016. 29(3): p. 354-63.
8. Basen-Engquist, K. and M. Chang, Obesity and cancer risk: recent review and
evidence. Curr Oncol Rep, 2011. 13(1): p. 71-6.
9. Chesi, A. and S.F. Grant, The Genetics of Pediatric Obesity. Trends Endocrinol
Metab, 2015. 26(12): p. 711-21.
10. Celis-Morales, C., et al., Can genetic-based advice help you lose weight?
Findings from the Food4Me European randomized controlled trial. 2017.
11. Nielsen, J., Systems Biology of Metabolism: A Driver for Developing
Personalized and Precision Medicine. Cell Metab, 2017. 25(3): p. 572-579.
12. Kornet-van der Aa, D.A., et al., The effectiveness and promising strategies of
obesity prevention and treatment programmes among adolescents from
disadvantaged backgrounds: a systematic review. Obes Rev, 2017.
13. Yanovski, S.Z. and J.A. Yanovski, Long-term drug treatment for obesity: a
systematic and clinical review. Jama, 2014. 311(1): p. 74-86.
14. Dietrich, M.O. and T.L. Horvath, Limitations in anti-obesity drug development:
the critical role of hunger-promoting neurons. Nat Rev Drug Discov, 2012. 11(9):
15. Martel, J., et al., Anti-obesogenic and antidiabetic effects of plants and
mushrooms. Nat Rev Endocrinol, 2017. 13(3): p. 149-160.
16. Gupta, S. and Z. Wang, Treatment satisfaction with different weight loss methods
among respondents with obesity. Clin Obes, 2016. 6(2): p. 161-70.
17. Saper, R.B., D.M. Eisenberg, and R.S. Phillips, Common dietary supplements for
weight loss. Am Fam Physician, 2004. 70(9): p. 1731-8.
18. Filippatos, T.D., et al., Orlistat-associated adverse effects and drug interactions:
a critical review. Drug Saf, 2008. 31(1): p. 53-65.
19. Manigault, K.R. and M.M. Thurston, Liraglutide: A Glucagon-Like Peptide-1
Agonist for Chronic Weight Management. Consult Pharm, 2016. 31(12): p.
20. Prasad-Reddy, L. and D. Isaacs, A clinical review of GLP-1 receptor agonists:
efficacy and safety in diabetes and beyond. Drugs Context, 2015. 4: p. 212283.
21. Hanipah, Z.N. and P.R. Schauer, Surgical Treatment of Obesity and Diabetes.
Gastrointest Endosc Clin N Am, 2017. 27(2): p. 191-211.
22. Hao, P.P., et al., Traditional Chinese medication for cardiovascular disease. Nat
Rev Cardiol, 2015. 12(2): p. 115-22.
23. Kong, L.Y. and R.X. Tan, Artemisinin, a miracle of traditional Chinese medicine.
Nat Prod Rep, 2015. 32(12): p. 1617-21.
24. Koehn, F.E. and G.T. Carter, The evolving role of natural products in drug
discovery. Nat Rev Drug Discov, 2005. 4(3): p. 206-20.
25. Fabricant, D.S. and N.R. Farnsworth, The value of plants used in traditional
medicine for drug discovery. Environ Health Perspect, 2001. 109 Suppl 1: p.
26. Kraft, K.H., et al., Multiple lines of evidence for the origin of domesticated chili
pepper, Capsicum annuum, in Mexico. Proc Natl Acad Sci U S A, 2014. 111(17):
27. Varghese, S., et al., Chili pepper as a body weight-loss food. Int J Food Sci Nutr,
2016: p. 1-10.
28. Richards, B.L., S.L. Whittle, and R. Buchbinder, Neuromodulators for pain
management in rheumatoid arthritis. Cochrane Database Syst Rev, 2012. 1: p.
29. Singh, U. and J.A. Bernstein, Intranasal capsaicin in management of nonallergic
(vasomotor) rhinitis. Prog Drug Res, 2014. 68: p. 147-70.
30. Zheng, L., et al., Capsaicin enhances anti-proliferation efficacy of pirarubicin via
activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells. Mol
Med Rep, 2016. 13(1): p. 881-7.
31. Liu, Y.P., et al., Role of Autophagy in Capsaicin-Induced Apoptosis in U251
Glioma Cells. Cell Mol Neurobiol, 2016. 36(5): p. 737-43.
32. Dairam, A., et al., Antioxidant and iron-binding properties of curcumin, capsaicin,
and S-allylcysteine reduce oxidative stress in rat brain homogenate. J Agric Food
Chem, 2008. 56(9): p. 3350-6.
33. Liu, J., et al., Treatment of obesity with celastrol. Cell, 2015. 161(5): p. 999-1011.
34. Wahlqvist, M.L. and N. Wattanapenpaiboon, Hot foods--unexpected help with
energy balance? Lancet, 2001. 358(9279): p. 348-9.
35. Snitker, S., et al., Effects of novel capsinoid treatment on fatness and energy
metabolism in humans: possible pharmacogenetic implications. Am J Clin Nutr,
2009. 89(1): p. 45-50.
36. Lejeune, M.P., E.M. Kovacs, and M.S. Westerterp-Plantenga, Effect of capsaicin
on substrate oxidation and weight maintenance after modest body-weight loss in
human subjects. Br J Nutr, 2003. 90(3): p. 651-59.
37. Inoue, N., et al., 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(2): p. 380-9.
38. Whiting, S., E. Derbyshire, and B.K. Tiwari, Capsaicinoids and capsinoids. A
potential role for weight management? A systematic review of the evidence.
Appetite, 2012. 59(2): p. 341-8.
39. Whiting, S., E.J. Derbyshire, and B. Tiwari, Could capsaicinoids help to support
weight management? A systematic review and meta-analysis of energy intake data.
Appetite, 2014. 73: p. 183-8.
40. Yoshioka, M., et al., Effects of red pepper on appetite and energy intake. Br J Nutr,
1999. 82(2): p. 115-23.
41. Yoneshiro, T. and M. Saito, Activation and recruitment of brown adipose tissue as
anti-obesity regimens in humans. Ann Med, 2015. 47(2): p. 133-41.
42. Saito, M. and T. Yoneshiro, Capsinoids and related food ingredients activating
brown fat thermogenesis and reducing body fat in humans. Curr Opin Lipidol,
2013. 24(1): p. 71-7.
43. Nirengi, S., et al., Assessment of human brown adipose tissue density during daily
ingestion of thermogenic capsinoids using near-infrared time-resolved
spectroscopy. J Biomed Opt, 2016. 21(9): p. 091305.
44. Chen, J., et al., Activation of TRPV1 channel by dietary capsaicin improves
visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc
Diabetol, 2015. 14: p. 22.
45. Sun, F., S. Xiong, and Z. Zhu, Dietary Capsaicin Protects Cardiometabolic
Organs from Dysfunction. Nutrients, 2016. 8(5).
46. Ludy, M.J. and R.D. Mattes, Comparison of sensory, physiological, personality,
and cultural attributes in regular spicy food users and non-users. Appetite, 2012.
58(1): p. 19-27.
47. Ma, L., et al., Activation of TRPV1 reduces vascular lipid accumulation and
attenuates atherosclerosis. Cardiovasc Res, 2011. 92(3): p. 504-13.
48. Gram, D.X., et al., Capsaicin-sensitive sensory fibers in the islets of Langerhans
contribute to defective insulin secretion in Zucker diabetic rat, an animal model
for some aspects of human type 2 diabetes. Eur J Neurosci, 2007. 25(1): p.
49. Wang, P., et al., Transient receptor potential vanilloid 1 activation enhances gut
glucagon-like peptide-1 secretion and improves glucose homeostasis. Diabetes,
2012. 61(8): p. 2155-65.
50. Kang, J.H., et al., Capsaicin, a spicy component of hot peppers, modulates
adipokine gene expression and protein release from obese-mouse adipose tissues
and isolated adipocytes, and suppresses the inflammatory responses of adipose
tissue macrophages. FEBS Lett, 2007. 581(23): p. 4389-96.
51. de Jong, P.R., et al., Ion channel TRPV1-dependent activation of PTP1B
suppresses EGFR-associated intestinal tumorigenesis. J Clin Invest, 2014. 124(9):
52. Hsu, C.L. and G.C. Yen, Effects of capsaicin on induction of apoptosis and
inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem, 2007. 55(5): p.
53. Zhang, L.L., et al., Activation of transient receptor potential vanilloid type-1
channel prevents adipogenesis and obesity. Circ Res, 2007. 100(7): p. 1063-70.
54. Kang, J.H., et al., Dietary capsaicin reduces obesity-induced insulin resistance
and hepatic steatosis in obese mice fed a high-fat diet. Obesity (Silver Spring),
2010. 18(4): p. 780-7.
55. Ohnuki, K., et al., Administration of capsiate, a non-pungent capsaicin analog,
promotes energy metabolism and suppresses body fat accumulation in mice.
Biosci Biotechnol Biochem, 2001. 65(12): p. 2735-40.
56. Villarroya, F., et al., Brown adipose tissue as a secretory organ. Nat Rev
Endocrinol, 2017. 13(1): p. 26-35.
57. Saito, M., T. Yoneshiro, and M. Matsushita, Food Ingredients as Anti-Obesity
Agents. Trends Endocrinol Metab, 2015. 26(11): p. 585-7.
58. Ohyama, K., et al., A combination of exercise and capsinoid supplementation
additively suppresses diet-induced obesity by increasing energy expenditure in
mice. Am J Physiol Endocrinol Metab, 2015. 308(4): p. E315-23.
59. Baskaran, P., et al., TRPV1 activation counters diet-induced obesity through
sirtuin-1 activation and PRDM-16 deacetylation in brown adipose tissue. Int J
Obes (Lond), 2017.
60. Baskaran, P., et al., Capsaicin induces browning of white adipose tissue and
counters obesity by activating TRPV1 channel-dependent mechanisms. Br J
Pharmacol, 2016. 173(15): p. 2369-89.
61. Ahima, R.S. and D.A. Antwi, Brain regulation of appetite and satiety. Endocrinol
Metab Clin North Am, 2008. 37(4): p. 811-23.
62. Ozcan, L., et al., Endoplasmic reticulum stress plays a central role in development
of leptin resistance. Cell Metab, 2009. 9(1): p. 35-51.
63. Myers, M.G., M.A. Cowley, and H. Munzberg, Mechanisms of leptin action and
leptin resistance. Annu Rev Physiol, 2008. 70: p. 537-56.
64. Lee, E., et al., Transient receptor potential vanilloid type-1 channel regulates
diet-induced obesity, insulin resistance, and leptin resistance. Faseb j, 2015. 29(8):
65. Janssens, P.L., R. Hursel, and M.S. Westerterp-Plantenga, Capsaicin increases
sensation of fullness in energy balance, and decreases desire to eat after dinner in
negative energy balance. Appetite, 2014. 77: p. 44-9.
66. Kawada, T., et al., Gastrointestinal absorption and metabolism of capsaicin and
dihydrocapsaicin in rats. Toxicol Appl Pharmacol, 1984. 72(3): p. 449-56.
67. Leung, F.W., Capsaicin-sensitive intestinal mucosal afferent mechanism and body
fat distribution. Life Sci, 2008. 83(1-2): p. 1-5.
68. Leung, F.W., et al., Stimulation of intestinal mucosal afferent nerves increases
superior mesenteric artery and decreases mesenteric adipose tissue blood flow.
Dig Dis Sci, 2001. 46(6): p. 1217-22.
69. Shen, W., et al., Anti-obesity Effect of Capsaicin in Mice Fed with High-Fat Diet
Is Associated with an Increase in Population of the Gut Bacterium Akkermansia
muciniphila. Front Microbiol, 2017. 8: p. 272.
Figure 1. The molecular structure of capsaicin and isolated from chili peppers.
Figure 2. Molecular mechanisms of the anti-obesity effects of capsaicin. A. Capsaicin
can inhibit adipogenesis in preadipocyte and adipocyte by up-regulating the expression of
PPARȖ and UCP-1. Thus, it will increase stimulate adiponectin secretion and increase
body fat accumulation; B. Capsaicin can activate BAT activity, accompanied by increased
expression of UCP-1 and PGC1-; C.Capsaicin can suppress appetite, increase satiety and
ameliorate insulin resistance; D. Capsaicin can modulate its function in gastrointestinal
tract and gut microbiome, including stimulate GLP-1 secretion and increase in population
of the gut bacterium Akkermansia muciniphila. BAT: brown adipose tissue; GLP-1:
glucagon-like peptide-1; Muc2: mucin 2 gene; PPARĮ: peroxisome proliferator activated
receptor Į; PPARȖ: peroxisome proliferator activated receptor Ȗ; PGC1-Į: PPARȖ
coactivator 1-Į; Reg3g: regenerating islet-derived protein 3 gamma; STAT-3: signal
transducer and activator of transcription-3; TRPV1: transient receptor potential vanilloid
1; UCP-1: uncoupling protein 1; WAT: white adipose tissue.
Table 1 | Clinical studies of the weight-loss effects of capsaicin
Treatments Year Country Study design Subjects
(6 mg per
day for 12
2009 USA Double-blind,
30.6±2.4 N=80 42±8 Body weight
None Increase in fat
10 g single
1999 Canada Prospective study Healthy
25.3±4.7 N=23 25.8±2.8 Decreases
None Increase in
et al .
per day for
2007 Japan Double-blind,
˚23 N=48 30–65 Body weight
the 2 to 4 week
None Increased VO2,
Inoue et al
(135 mg per
day for 3
2003 Netherlands Randomized
29.3±2.5 N=140 18-60 Significant
None More sustained
(9 mg per
day for 8
2016 Japan Randomized
N=20 20.7±1.2 Increased
et al .
Table 2 | Pre-clinical studies aboutanti-obesity effects of capsaicin
Treatments Species Duration Metabolic disorders Potential Mechanism Reference
24-72 hour - decreased the amount of
intracellular triglycerides, GPDH
- induced apoptosis;
- inhibited adipogenesis;
- inhibited the expression of PPARȖ,
C/EBP-Į, and leptin;
- induced up-regulation of adiponectin
at the protein level;
Hsu et al .
1 umol/L Capsaicin 3T3-L1-preadipo
3-8 days - prevented the adipogenesis - increased intracellular calcium Zhang et al
0.015% Capsaicin Male C57BL/6
10 weeks - decreased triglyceride levels;
- lowered fasting glucose, insulin,
- decreased TRPV-1 expression in
- increased mRNA/protein of
adiponectin in the adipose tissue;
- increased PPARĮ/PGC-1Į mRNA in
Kang et al .
Std ddY mice 2 weeks - lower body weight;
- markedly suppressed body fat
- decreased triglyceride levels;
- increased oxygen consumption;
- stimulated the secretion of adrenalin;
Ohnuki et al
0.3% Capsinoids C57BL/6J mice 8 weeks - suppressed body weight gain under
- decreased plasma cholesterol level;
- prevented diet-induced liver
- increased energy expenditure;
- activation of fat oxidation in skeletal
- activation lipolysis in BAT;
- increased cAMP levels and PKA
activity in BAT;
Ohyama et al
0.003%, 0.01% and
16 weeks - promoted weight loss;
- enhanced the respiratory exchange
- countered hypercholesterolemia;
- increased the expression UCP-1,
BMP8b, SIRT-1, PGC-1Į and
prdm-16 in BAT;
- increased the phosphorylation of
Baskaran et al
0.01% Capsaicin wild-type and
26 weeks - countered obesity;
- browning of WAT;
- promoted sirtuin-1 expression;
- increased the expression of PGC-1Į;
- facilitated PPARȖ-PRDM-16
Baskaran et al
0.01% Capsaicin wild-type and
24 weeks - ameliorated abnormal glucose
- increased GLP-1 levels in the
plasma and ileum;
- activation of TRPV1-mediated GLP-1
secretion in the intestinal cells;
Wang et al
640 umol/L, 2 ml/kg
15min - increased superior mesenteric artery
- reduction in hydrogen gas
- induced a dichotomous pattern of
blood flow changes;
Leung et al
0.01% Capsaicin C57BL/6J male
9 weeks - reduced weight gain;
- improved glucose tolerance;
- modest modulation of the gut
- up-regulated the expression of Mucin
2 gene and antimicrobial protein gene
Reg3g in the intestine;
Shen et al .
BAT, brown adipose tissue; BMP8b, bone morphogenetic protein-8b; cAMP, cyclic adenosine monophosphate; C/EBP-Į, CCAAT-enhancer-binding protein-Į;
PKA, protein kinase A; GLP-1, glucagon-like peptide-1; GPDH, glycerol-3-phosphate dehydrogenase; PPARĮ, peroxisome proliferator activated receptor Į;
PPARȖ, peroxisome proliferator activated receptor-Ȗ; PRDM-16, positive regulatory domain containing 16; PGC1-Į, PPARȖ coactivator 1-Į; SIRT-1, sirtuin-1;
TRPV1, transient receptor potential vanilloid 1; UCP-1, uncoupling protein 1; WAT, white adipose tissue.