Cayenne

• How It Works

  Oral cayenne may provide limited relief of mucositis pain caused by radiation treatment, but it may cause gastric side effects in certain concentrations.

  The capsicum pepper contains a chemical called capsaicin that is a powerful irritant. Because this compound can affect nerves that report painful stimuli to the brain, it has become useful in some forms such as over-the-counter creams for some skin conditions and nerve pain. Oral forms have been marketed for circulation problems, poor appetite, and weight loss, but there are no studies to confirm such effects. It may be helpful for pain from mucositis caused by cancer therapy, but the study had a very small number of patients enrolled and effects were incomplete and temporary.

• Purported Uses
  • To relieve colic and stomach/intestinal gas
    No scientific evidence supports this use. The capsicum pepper is known to be a gastrointestinal stimulant and irritant.
  • To treat diarrhea
    This claim is not backed by data. In certain amounts, it may actually cause diarrhea.
  • To treat headaches
    Laboratory data show that capsaicin blocks pain fibers, but whether it can treat headaches is unknown.
  • To lower high cholesterol
    No scientific evidence supports this use.
  • To manage type 2 diabetes
    Capsaicin may help to maintain insulin levels and lower blood glucose levels. Further study is needed.
  • To improve circulation
    Although cayenne is traditionally used for circulation, clinical trial data are lacking.
  • To treat burning mouth syndrome
    A pilot study showed benefit, however, significant side effects were also noted.
  • To treat oral inflammation
    A small study shows limited benefit to treat mucositis pain from cancer therapy.
  • To treat stomach and intestinal gas
    Although capsaicin has traditionally been used for digestive issues, research is lacking.
  • Weight management
    Any effect of capsaicin on weight management appears to be small. 
• Do Not Take If
  • You are taking ACE inhibitors: Can increase the incidence of cough that is associated with ACE inhibitors.
  • You are taking blood-thinning medications: Capsaicin may have antiplatelet effects.
  • You are taking blood pressure medications: Capsaicin may lessen its effects.
  • You are taking immunosuppressants: Capsaicin may increase its bioavailability.
  • You are taking drugs that are substrates of P-glycoprotein: Capsaicin may affect how these drugs are absorbed or metabolized.
  • You are taking drugs that are substrates of Cytochrome P450 3A: Capsaicin may affect how these drugs are absorbed or metabolized.
  • You are taking theophylline: Capsaicin may increase its absorption.
  • You are taking other prescription drugs: Capsaicin may interfere with their absorption.
  • You have poorly controlled blood pressure, heart disease, or other vascular conditions.
  • You are pregnant or breastfeeding: May cause skin redness in nursing babies.
• Side Effects

  Sweating and flushing, irritation of the eyes and nose. In large doses, capsicum can cause irritation of the gastrointestinal tract or increase blood pressure.

  Case Reports

  • High blood pressure in two men after they ate large amounts of chili peppers.
  • Gastric cell exfoliations and bleeding after dietary intakes of capsicum in healthy volunteers.
  • Skin rash/redness in two infants shortly after being breastfed by mothers who ate food spiced with red pepper.
• Scientific Name

  Capsicum frutescens, Capsicum annuum. Family: Solanaceae

• Clinical Summary

  Derived from the fruit of Capsicum, cayenne is among the most widely consumed culinary spice. Traditionally, it is used as a gargle for laryngitis and orally as a gastrointestinal stimulant. Oral formulations are marketed largely for digestive and circulatory problems, poor appetite, and weight loss. The active component, capsaicin, is also marketed for topical use to relieve various types of pain and for certain skin conditions (See Capsaicin topical formulations).

  Capsaicin may increase insulin and decrease blood glucose levels ⁽¹⁾. Nonpungent capsaicin analogues can produce a stimulatory effect in humans, but their potential role in energy expenditure and weight management problems needs further clarification ^{(2) (3) (4)}. In addition, the thermogenic and appetitive effects of capsaicin have been determined to be small ⁽⁵⁾. Oral capsaicin administered to participants in one study enhanced salty taste sensations, thereby lowering daily salt intake and subsequent blood pressure ⁽²⁹⁾. A preliminary study of enteric-coated oral capsaicin suggests it may decrease visceral hyperalgesia and improve bloating in patients with irritable bowel syndrome ⁽⁶⁾. Supplementation with capsicum for burning mouth syndrome is associated with significant side effects ⁽⁷⁾.

  Another study of oral capsaicin suggests that it can alleviate oral mucositis pain from cancer therapy, but this relief was temporary and not complete ⁽⁸⁾. There is continued controversy over whether active constituents of capsicum act as a carcinogen, co-carcinogen, or anti-carcinogen ^{(9) (10) (11) (12)} , and effects may be concentration-dependent ⁽⁹⁾. In vitro studies have shown cytotoxic effects against breast ⁽¹³⁾, bladder ⁽¹⁴⁾, prostate ⁽¹⁵⁾, and oral cancer cell lines ⁽¹⁶⁾, and multidrug-resistant lymphoma ⁽¹⁷⁾. However, a human case-control study suggests an increased risk for gastric cancer with dietary capsaicin ⁽¹⁸⁾. Therefore, more studies are needed to clarify the roles of capsaicin in relationship to cancer.

• Food Sources

  Fruits of capsicum pepper

• Purported Uses
  • Burning mouth syndrome
  • Circulatory disorders
  • Colic
  • Headaches
  • High cholesterol
  • Motion sickness
  • Mucositis
  • Spasms
  • Stomach and intestinal gas
  • Weight management
• Mechanism of Action

  Capsaicin is the compound responsible for the irritant effects of capsicum ⁽¹⁰⁾. Perceived heat from capsaicin when ingesting cayenne is caused by activation of transient receptor potential vanilloid subfamily member 1 (TRPV1), located in neurons on the tongue ⁽⁴⁾. Capsinoids lack this sensory quality because they are hydrolyzed as they cross the oral mucosa ⁽⁴⁾. Potential thermogenic effects also involve activation of TRPV1 receptors on vagal afferents in the gut ⁽⁴⁾. Capsaicin may induce energy expenditure by enhancing core body and skin temperature and influencing substrate oxidation, but these effects can vary with body composition ^(3) (5). In response to high-salt stimuli, oral capsaicin administration enhanced insula and orbitofrontal cortex (OFC) metabolic activity in participants, reversing salt intensity-dependent differences in the metabolism of the insula and OFC ⁽²⁹⁾.

  It was also found to induce coronary vasodilation by releasing calcitonin gene-related peptide (CGRP), a potent vasodilator. Depletion in CGRP leads to a subsequent increase in blood pressure ⁽²¹⁾. Interactions between capsaicin and cyclosporin indicate the ability of capsaicin to modulate P-gp and CYP3A gene expression and to also increase cyclosporin bioavailability via CYP3A inhibition ⁽²²⁾. Lignan glycosides isolated from capsicum pepper were also shown to have strong scavenging activity against the free radical, DPPH ⁽²⁰⁾.

  In vitro and animal studies indicate capsaicin causes cell-cycle arrest and apoptosis in both ER+ and ER− breast cancer cells by modulating the EGFR/HER-2 pathway ⁽¹³⁾. Orally administered capsaicin also slowed the growth of PC-3 prostate cancer cells in mice by downregulating expression of androgen receptors and by a direct inhibitory effect on prostate specific antigen transcription ⁽¹⁵⁾. In bladder cancer, capsaicin mediates cell death through reactive oxygen species (ROS) production and mitochondrial depolarization ⁽¹⁴⁾. Conversely, in certain concentrations, capsaicin may promote colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways ⁽⁹⁾.

• Contraindications

  Women who are pregnant or breastfeeding, as there have been case reports of dermatitis in nursing infants ⁽²³⁾.

• Adverse Reactions

  Common (oral): GI irritation, referred gastric pain ⁽⁷⁾.

  Case Reports
  Arterial hypertension: Reported in two men following ingestion of large amounts of chili peppers ^(21) (24).
  Gastric cell exfoliation and bleeding: Ingestion of dietary capsicum in healthy volunteers caused gastric cell exfoliation and bleeding ⁽²⁵⁾.
  Erythematous dermatitis: Reported in two infants shortly after breastfeeding from mothers who had ingested food flavored with red pepper ⁽²³⁾.

• Herb-Drug Interactions

  ACE inhibitors: Capsaicin may increase the incidence of cough associated with ACE inhibitors ⁽²⁶⁾.
  Antihypertensives: Capsaicin may affect their actions ⁽²¹⁾.
  Antiplatelet drugs: Animal models indicate capsaicin has antiplatelet effects ⁽²⁷⁾.
  Cytochrome P450 (CYP) 3A substrates: Capsaicin may alter drug absorption and metabolism ⁽²²⁾. Immunosuppressants (cyclosporin): Concurrent capsaicin should be avoided for transplant patients in order to minimize the risk for nephrotoxicity, hepatotoxicity and neurotoxicity. In animal models, chronic high-dose capsaicin use increased cyclosporin bioavailability ⁽²²⁾.
  P-glycoprotein (P-gp) substrates: Capsaicin may alter drug absorption and metabolism ⁽²²⁾.
  Theophylline: Animal models indicate that concurrent capsaicin administration may increase absorption ⁽²⁸⁾.
  Oral co-administration of other drugs: Capsaicin causes mucosal vasodilation, thereby altering the uptake of other drugs ⁽²²⁾.

• References

  1. Chaiyasit K, Khovidhunkit W, Wittayalertpanya S. Pharmacokinetic and the effect of capsaicin in Capsicum frutescens on decreasing plasma glucose level. J Med Assoc Thai. Jan 2009;92(1):108-113.

  2. Whiting S, Derbyshire E, Tiwari BK. Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of the evidence. Appetite. Oct 2012;59(2):341-348.

  3. Yoneshiro T, Aita S, Kawai Y, et al. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr. Apr 2012;95(4):845-850.

  4. Snitker S, Fujishima Y, Shen H, et al. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. Am J Clin Nutr. Jan 2009;89(1):45-50.

  5. 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. Feb 2012;37(2):103-121.

  6. Bortolotti M, Porta S. Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study. Dig Dis Sci. Nov 2011;56(11):3288-3295.

  7. Petruzzi M, Lauritano D, De Benedittis M, et al. Systemic capsaicin for burning mouth syndrome: short-term results of a pilot study. J Oral Pathol Med. Feb 2004;33(2):111-114.

  8. Berger A, Henderson M, Nadoolman W, et al. Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy. J Pain Symptom Manage. Apr 1995;10(3):243-248.

  9. Yang J, Li TZ, Xu GH, et al. Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma. 2013;60(4):364-372.

  10. Bode AM, Dong Z. The two faces of capsaicin. Cancer Res. Apr 15 2011;71(8):2809-2814.

  11. Lin CH, Lu WC, Wang CW, et al. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Altern Med. 2013;13:46.

  12. Hwang MK, Bode AM, Byun S, et al. Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1. Cancer Res. Sep 1 2010;70(17):6859-6869.

  13. Thoennissen NH, O’Kelly J, Lu D, et al. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene. Jan 14 2010;29(2):285-296.

  14. Yang ZH, Wang XH, Wang HP, et al. Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology. Mar 2010;75(3):735-741.

  15. Mori A, Lehmann S, O’Kelly J, et al. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res. Mar 15 2006;66(6):3222-3229.

  16. Motohashi N, Wakabayashi H, Kurihara T, et al. Cytotoxic and multidrug resistance reversal activity of a vegetable, ’Anastasia Red’, a variety of sweet pepper. Phytother Res. Apr 2003;17(4):348-352.

  17. Motohashi N, Kurihara T, Wakabayashi H, et al. Biological activity of a fruit vegetable, “Anastasia green”, a species of sweet pepper. In Vivo. Sep-Oct 2001;15(5):437-442.

  18. Lopez-Carrillo L, Lopez-Cervantes M, Robles-Diaz G, et al. Capsaicin consumption, Helicobacter pylori positivity and gastric cancer in Mexico. Int J Cancer. Aug 20 2003;106(2):277-282.

  19. Wahyuni Y, Ballester AR, Sudarmonowati E, et al. Metabolite biodiversity in pepper (Capsicum) fruits of thirty-two diverse accessions: variation in health-related compounds and implications for breeding. Phytochemistry. Aug 2011;72(11-12):1358-1370.

  20. Lee DY, Lee DG, Cho JG, et al. Lignans from the fruits of the red pepper (Capsicum annuum L.) and their antioxidant effects. Arch Pharm Res. Oct 2009;32(10):1345-1349.

  21. Patane S, Marte F, Di Bella G, et al. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone. Int J Cardiol. May 1 2009;134(1):130-132.

  22. Zhai XJ, Shi F, Chen F, et al. Capsaicin pretreatment increased the bioavailability of cyclosporin in rats: Involvement of P-glycoprotein and CYP 3A inhibition. Food Chem Toxicol. Sep 4 2013;62C:323-328.

  23. Cooper RL, Cooper MM. Red pepper-induced dermatitis in breast-fed infants. Dermatology. 1996;193(1):61-62.

  24. Patane S, Marte F, La Rosa FC, et al. Capsaicin and arterial hypertensive crisis. Int J Cardiol. Oct 8 2010;144(2):e26-27.

  25. Myers BM, Smith JL, Graham DY. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol. Mar 1987;82(3):211-214.

  26. Hakas JF, Jr. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy. Oct 1990;65(4):322-323.

  27. Wang JP, Hsu MF, Teng CM. Antiplatelet effect of capsaicin. Thromb Res. Dec 15 1984;36(6):497-507.

  28. Bouraoui A, Toumi A, Ben Mustapha H, et al. Effects of capsicum fruit on theophylline absorption and bioavailability in rabbits. Drug Nutr Interact. 1988;5(4):345-350.

  29. Li Q, Cui Y, Jin R, et al. Enjoyment of Spicy Flavor Enhances Central Salty-Taste Perception and Reduces Salt Intake and Blood Pressure. Hypertension. Dec 2017;70(6):1291-1299.