A review of the effects of Capsicum annuum L. and its constituent, capsaicin, in metabolic syndrome

Document Type : Review Article


1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): Metabolic syndrome, a coexisting of high blood glucose, obesity, dyslipidemia and hypertension, is an important risk factor for cardiovascular disease occurrence and mortality. Recently, there is a rising demand for herbal drugs which have less adverse effects and have shown more beneficial effects in comparison with synthetic options. Red pepper, with the scientific name of Capsicum annuum, belongs to the Solanaceae family. The lipid-lowering, antihypertensive, antidiabetic and anti-obesity effects of C. annuum have been demonstrated in several studies.
Materials and Methods:  In this review, we summarized different animal and human studies on the effect of red pepper and capsaicin on different components of metabolic syndrome which are risk factors for cardiovascular diseases (CVDs).
Results: According to these studies, red pepper as well as capsaicin has ability to control of metabolic syndrome and its related disorders such as obesity, disrupted lipid profile, diabetes and its complications.
Conclusion: Red pepper has beneficial effects on metabolic syndrome and can decrease the risk of mortality due to cardiovascular diseases, but still more research projects need to be done and confirm its advantageous especially in humans.


Main Subjects

1. Marjani A.  A Review on metabolic syndrome. J Endocrinol Metab 2012; 2:166-170.
2. Jungbauer A, Medjakovic S. Anti-inflammatory properties of culinary herbs and spices that ameliorate the effects of metabolic syndrome. Maturitas 2012; 71:227-239.
3. Akaberi M, Hosseinzadeh H . Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the Metabolic Syndrome. Phtother Res 2016; 30:540-556.
4. Razavi B, Hosseinzadeh H. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 2014; 37:1031–1040.
5.    Hosseini A, Hosseinzadeh H . A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest 2015; 38:1147-1157.
6.    Vahdati Hassani F, Shirani K, Hosseinzadeh H . Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: a review. Naunyn-Schmiedeberg’s Arch Pharmacol 2016; 389:931-949.
7.    Tabeshpour J, Razavi BM, Hosseinzadeh H.  Effects of avocado (Persea americana) on metabolic syndrome: a comprehensive systematic review. Phytother Res 2017; 31:819-837.
8.    Tabeshpour J, Imenshahidi M, Hosseinzadeh H . A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci 2017; 20:557-568.
9.    Mollazadeh H, Hosseinzadeh H . Cinnamon effects on metabolic syndrome: a review based on its mechanisms. Iran J Basic Med Sci 2016; 19:1258-1270.
10.    Hosseinzadeh H, Nassiri-Asl M . Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J Endocrinol Invest 2014; 37:783–788.
11.    Razavi B, Hosseinzadeh H . Saffron: a promising natural medicine in the treatment of metabolic syndrome. J Sci Food Agric 2016; 97: 1679–1685.
12.     Tousian Shandiz H, Razavi BM, Hosseinzadeh H. Review of Garcinia mangostana and its xanthones in metabolic syndrome and related complications. Phytother Res 2017; 31:1173-1182.
13.    Razavi BM, Lookian F, Hosseinzadeh H. Protective effects of green tea on olanzapine-induced-metabolic syndrome in rats. Biomed Pharmacother 2017; 92: 726-731.
14.    Barceloux DG. Pepper and capsaicin (Capsicum and Piper species). Dis Mon 2009; 55:380-390.
15.    Singletary K . Red pepper: overview of potential health benefits. Nut Today 2011; 46:33-47.
16.    Pawar SS, Bharude NV, Sonone SS, Deshmukh RS, Raut AK, Umarkar AR . Chilles as food, spice and medicine: a perspective. Int J Pharm Biol Sci  2011; 1: 311-318.
17.    Maji AK, Banerji P. Phytochemistry and gastrointestinal benefits of the medicinal spice, Capsicum annuum L.(Chilli): a review. J Complement Integr Med 2016; 13:97-122.
18.    Low Dog T .  A reason to season: the therapeutic benefits of spices and culinary herbs. Explore (NY) 2006; 2:446-449.
19.    Kim W-R, Kim EO, Kang K, Oidovsambuu S, Jung SH, Kim BS,  et al. Antioxidant activity of phenolics in leaves of three red pepper (Capsicum annuum) cultivars. J Agric Food Chem 2014; 62:850-859.
20.    Ludy M-J, 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; 37:103-21.
21.    Papoiu AD, Yosipovitch G . Topical capsaicin. The fire of a ‘hot’medicine is reignited. Expert Opin Pharmacother 2010; 11:1359-1371.
22.    Hayman M, Kam PC . Capsaicin: a review of its pharmacology and clinical applications. Curr Anaesth  Crit Care 2008; 19:338-343.
23.    Srinivasan K . Spices as influencers of body metabolism: an overview of three decades of research. Food Res Int 2005; 38:77-86.
24.    Wesolowska A, Jadczak D, Grzeszczuk M. Chemical composition of the pepper fruit extracts of hot cultivars Capsicum annuum L. Acta Sci Pol Hortorum Cultus 2011; 10:171-184.
25.    D’Alonzo AJ, Grover GJ, Darbenzio RB, Hess TA, Sleph PG, Dzwonczyk S, et al . In vitro effects of capsaicin: antiarrhythmic and antiischemic activity. Eur J Pharmacol 1995; 272:269-278.
26.    Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004; 328:991.
27.    Mueller M, Beck V, Jungbauer A . PPARalpha activation by culinary herbs and spices. Planta Med 2011; 77:497-504.
28.    Negulesco J A, Noel S A, Newman, H A I .  Effect of pure capsaicinoids (capsaicin and dihydrocapsaicin) on plasma lipids and lipoprotein concentrations of turmey poults. Atherosclerosis 1987; 64:85–90.
29.    Kempaiah RK, Srinivasan K. Beneficial influence of dietary curcumin, capsaicin and garlic on erythrocyte integrity in high-fat fed rats. J Nutr Biochem 2006; 17:471-478.
30.    Pande S, Srinivasan K. Potentiation of hypolipidemic and weight-reducing influence of dietary tender cluster bean (Cyamopsis tetragonoloba) when combined with capsaicin in high-fat-fed rats. J Agric Food Chem 2012; 60:8155-8162.
31.    Otunola G, Oloyede O, Oladiji A, Afolayan A . Hypolipidemic effect of aqueous extracts of selected spices and their mixture on diet-induced hypercholesterolemia in Wistar rats. Can J Pure Appl Sci 2012; 6:2063-2071.
32.    Kwon MJ, Song YS, Choi MS, Song YO . Red pepper attenuates cholesteryl ester transfer protein activity and atherosclerosis in cholesterol-fed rabbits. Clin Chim Acta 2003; 332:37-44.
33.    Manjunatha H, Srinivasan K. Hypolipidemic and antioxidant effects of dietary curcumin and capsaicin in induced hypercholesterolemic rats. Lipids 2007; 42:1133-1142.
34.    Kim Y, Park Y-J, Yang S-O, Kim S-H, Hyun S-H, Cho S,  et al. Hypoxanthine levels in human urine serve as a screening indicator for the plasma total cholesterol and low-density lipoprotein modulation activities of fermented red pepper paste. Nut Res 2010; 30:455-461.
35.    Lim J-H, Jung E-S, Choi E-K, Jeong D-Y, Jo S-W, Jin J-H, et al. Supplementation with Aspergillus oryzae-fermented kochujang lowers serum cholesterol in subjects with hyperlipidemia. Clin Nut 2015; 34:383-387.
36.    Ilevbare FR, Okparume DE, Erhirhie EO, O. EL . The roles of capsicum in diabetes mellitus. Wilolud J 2013; 6:22-27.
37.    Watcharachaisoponsiri T, Sornchan P, Charoenkiatkul S, Suttisansanee U . The α-glucosidase and α-amylase inhibitory activity from different chili pepper extracts. Int Food Res J 2016; 23:1439-1445.
38.    Tundis R, Loizzo MR, Menichini F, Bonesi M, Conforti F, Statti G, et al . Comparative study on the chemical composition, antioxidant properties and hypoglycaemic activities of two Capsicum annuum L. cultivars (Acuminatum small and Cerasiferum). Plant Foods Hum Nutr 2011; 66:261-269.
39.    Earnest EO, Lawrence E, Ilevbare FR. The roles of capsicum in diabetes mellitus. Wilolud J 2013; 6:22 -27.
40.    Sun F, Xiong S, Zhu Z. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction. Nutrients 2016; 8.
41.    Magied MMA, Salama NAR, Ali MR. Hypoglycemic and Hypocholesterolemia Effects of Intragastric Administration of Dried Red Chili Pepper (Capsicum Annum) in Alloxan-Induced Diabetic Male Albino Rats Fed with High-Fat-Diet. J Food Nut Res 2014; 2:850-856.
42.    Roghani M, Baluchnejadmojarad T, Sohrabi Z, Sadeghi M. Anti-hyperlycemic and hypolipidemic effect of oral administration of Capsicum frutescens in male STZ-diabetic rats. J Med Plants 2004; 2:47-52.
43.    Chen L, Kang Y-H . In Vitro Inhibitory Potential Against Key Enzymes Relevant for Hyperglycemia and Hypertension of Red Pepper (Capsicum annuum L.) Including Pericarp, Placenta, and Stalk. J Food Biochem 2014; 38:300-306.
44.    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.
45.    Yuan LJ, Qin Y, Wang L, Zeng Y, Chang H, Wang J, et al. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns. Clin Nutr 2016; 35:388-393.
46.    Deng PY, Li YJ. Calcitonin gene-related peptide and hypertension. Peptides 2005; 26:1676-1685.
47.    Zhang MJ, Yin YW, Li BH, Liu Y, Liao SQ, Gao CY, et al. The role of TRPV1 in improving VSMC function and attenuating hypertension. Prog Biophys Mol Biol 2015; 117:212-216.
48.    Adefegha SA, Oboh G. Phytochemistry and mode of action of some tropical spices in the management of type-2 diabetes and hypertension. African J Pharm Pharmacol 2013; 7:332-46.
49.    Jeon G, Choi Y, Lee S-M, Kim Y, Jeong H-S, Lee J.  Antiobesity activity of methanol extract from hot pepper (Capsicum annuum L.) seeds in 3T3-L1 adipocyte. Food Sci Biotechnol 2010; 19:1123-1127.
50.    Virus RM, Knuepfer MM, McManus DQ, Brody MJ, Gebhart GF. Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on nociceptive behavior and cardiovascular regulation. Eur J Pharmacol 1981; 72:209-217.
51.    Rioux F, Lemieux M, Roy G. Capsaicin-sensitive primary afferents are involved in the hypotensive effect of neurotensin in ganglion-blocked guinea pigs. Peptides 1989; 10:1033-40.
52.    Wimalawansa SJ. The effects of neonatal capsaicin on plasma levels and tissue contents of CGRP. Peptides 1993; 14:247-252.
53.    Lukovic L, de Jong W, de Wied D. Cardiovascular effects of substance P and capsaicin microinjected into the nucleus tractus solitarii of the rat. Brain Res 1987; 422:312-318.
54.    Massi M, Polidori C, Perfumi M, Ciccocioppo R, De Caro G, Bacciarelli C, et al. Effect of capsaicin neonatal treatment on the salt intake of the adult rat. Pharmacol Biochem Behav 1991; 40:163-168.
55.    Perez H, Ruiz S, Soto-Moyano R. Prenatal malnutrition-induced hypertension in young rats is prevented by neonatal capsaicin treatment. Neurosci Lett 2002; 328:253-256.
56.    Potenza MA, De Salvatore G, Montagnani M, Serio M, Mitolo-Chieppa D. Vasodilatation induced by capsaicin in rat mesenteric vessels is probably independent of nitric oxide synthesis. Pharmacol Res 1994; 30:253-261.
57.    Yang D, Luo Z, Ma S, Wong WT, Ma L, Zhong J, et al . Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab 2010; 12:130-141.
58.    Sessa WC. A new way to lower blood pressure: pass the chili peppers please! Cell Metab 2010; 12:109-110.
59.    Wang Q, Ma S, Li D, Zhang Y, Tang B, Qiu C, et al. Dietary capsaicin ameliorates pressure overload-induced cardiac hypertrophy and fibrosis through the transient receptor potential vanilloid type 1. Am J Hypertens 2014; 27:1521-1529.
60.    Kwon Y-I, Apostolidis E, Shetty K. Evaluation of pepper (Capsicum annum) for management of diabetes and hypertension.  J  Food Biochem 2007; 31:370-385.
61.    Patane S, Marte F, La Rosa FC, La Rocca R . Capsaicin and arterial hypertensive crisis. Int J Cardiol 2010, 144:e26-27.
62.    Patane S, Marte F, Di Bella G, Cerrito M, Coglitore S. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone. Int J Cardiol 2009; 134:130-132.
63.    Dutta A, Deshpande SB.  Mechanisms underlying the hypertensive response induced by capsaicin. Int J Cardiol 2010; 145:358-359.
64.    Baek J, Lee J, Kim K, Kim T, Kim D, Kim C, et al. Inhibitory effects of Capsicum annuum L. water extracts on lipoprotein lipase activity in 3T3-L1 cells. Nutr Res Pract 2013; 7:96-102.
65.    Gamboa-Gomez CI, Rocha-Guzman NE, Gallegos-Infante JA, Moreno-Jimenez MR, Vazquez-Cabral BD, Gonzalez-Laredo RF. Plants with potential use on obesity and its complications. Excli J 2015; 14:809-831.
66.    Woo H-M, Kang J-H, Kawada T, Yoo H, Sung M-K, Yu R. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes. Life Sci 2007; 80:926-931.
67.    Reinbach HC, Smeets A, Martinussen T, Møller P, Westerterp-Plantenga M. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance. Clin Nut 2009; 28:260-265.
68.    Zhang H, Matsuda H, Nakamura S, Yoshikawa M. Effects of amide constituents from pepper on adipogenesis in 3T3-L1 cells. Bioorg Med  Chem Lett 2008; 18:3272-3277.
69.    Marrelli M, Menichini F, Conforti F. Hypolipidemic and Antioxidant Properties of Hot Pepper Flower (Capsicum annuum L.). Plant Foods Hum Nutr 2016; 71:301-306.
70.    Do MS, Hong SE, Ha JH, Choi SM, Ahn IS, yoon JY,  et al . Increased lipolytic activity by high-pungency red pepper extract (var. chungyang) in rat adipocytes in vitro. J Food Sci Nutr 2004; 9:34-38.
71.    Hwang J-T, Park I-J, Shin J-I, Lee YK, Lee SK, Baik HW, et al . Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 2005; 338:694-699.
72.    Kang J-H, Kim C-S, Han I-S, Kawada T, Yu R. 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; 581:4389-4396.
73.    Leung FW. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution. Life Sci 2008; 83:1-5.
74.    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.
75.    Tan S, Gao B, Tao Y, Guo J, Su Z-q . Antiobese Effects of Capsaicin–Chitosan Microsphere (CCMS) in Obese Rats Induced by High Fat Diet. J Agr Food Chem 2014; 62:1866-74.
76.    Falchi M, Bertelli A, Ferrara F, Galazzo R, Galazzo S, Gharib C. et al . Intracerebroventricular capsaicin influences the body weight increasing of rats. Brain Res Bull 2008; 77:253-256.
77.    Lee GR, Shin MK, Yoon DJ, Kim AR, Yu R, Park NH, et al. Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high‐fat diet‐induced obese mice. Obesity 2013; 21:115-122.
78.    Sung J, Lee J.  Capsicoside G, a furostanol saponin from pepper (Capsicum annuum L.) seeds, suppresses adipogenesis through activation of AMP-activated protein kinase in 3T3-L1 cells. J Funct Foods 2016; 20:148-158.
79.    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.
80.    Yoshioka M, Imanaga M, Ueyama H, Yamane M, Kubo Y, Boivin A, et al . Maximum tolerable dose of red pepper decreases fat intake independently of spicy sensation in the mouth. Br J Nut 2004; 91:991-995.
81.    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 199880:503-510.
82.    Westerterp-Plantenga M, Diepvens K, Joosen AM, Berube-Parent S, Tremblay A.  Metabolic effects of spices, teas, and caffeine. Physiol Behav 200689:85-91.
83.    Smeets AJ, Westerterp-Plantenga MS. The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety. Eur J Nutr 2009; 48:229-234.
84.    Nieman DC, Cialdella-Kam L, Knab AM, Shanely RA.  Influence of red pepper spice and turmeric on inflammation and oxidative stress biomarkers in overweight females: a metabolomics approach. Plant Foods Hum Nutr 2012; 67:415-421.
85.    Ohnuki K, Niwa S, Maeda S, Inoue N, Yazawa S, Fushiki T.  CH-19 sweet, a non-pungent cultivar of red pepper, increased body temperature and oxygen consumption in humans. Biosci Biotechnol Biochem 20016; 5:2033-2036.
86.    Hachiya S, Kawabata F, Ohnuki K, Inoue N, Yoneda H, Yazawa S, et al.  Effects of CH-19 Sweet, a non-pungent cultivar of red pepper, on sympathetic nervous activity, body temperature, heart rate, and blood pressure in humans. Biosci Biotechnol Biochem 2007; 71:671-676.
87.    Yang HJ, Kwon DY, Kim MJ, Kim DS, Kang S, Shin BK, et al. Red peppers with different pungencies and bioactive compounds differentially modulate energy and glucose metabolism in ovariectomized rats fed high fat diets. J Funct Foods 2014; 7:246-256.
88.    Fernandez-Lopez JA, Remesar X, Foz M, Alemany M.  Pharmacological approaches for the treatment of obesity. Drugs 2002; 62:915-944.