Cinnamon

• How It Works

  Current evidence suggests benefits of cinnamon for lowering glucose, cholesterol and triglyceride levels.

  Cinnamon refers to several plants native to Southeast Asia. The bark, rich in essential oil, is used as a flavoring agent and as a spice. Cinnamon has a long history of use as an herbal medicine. Laboratory studies have shown that cinnamon has antibacterial, anti-inflammatory, and antioxidant properties. It was also shown to lower blood glucose levels in patients with type 2 diabetes, to lower total cholesterol and triglyceride levels, to reduce dental plaque and gingivitis, and to improve metabolic syndrome (metabolic disorders that increase the risk of cardiovascular disease, stroke and diabetes). Topical use of a cinnamon containing ointment was shown to help relieve perineal pain and improved healing of episiotomy incision in postpartum women.

• Purported Uses
  • Diabetes
    A systematic reviews and meta analysis showed that cinnamon is useful in lowering blood glucose, lipids, and insulin levels
  • Inflammation
    Laboratory studies showed that cinnamon can reduce inflammation. Human data are lacking.
  • Arthritis
    Cinnamon is used in traditional medicine for arthritis but there is no scientific evidence to support this claim.
• Patient Warnings

  Some cinnamon products contain high levels of coumarin, a natural constituent, that can cause liver damage.

• Do Not Take If
  • Cytochrome P450 2C9 , 3A4, 2A6, 2D substrates: Cinnamon may increase the risk of side effects of these drugs.
  • Statins: When taken along with statins, cinnamon has been reported to cause hepatitis.
  • Pioglitazone: When used together, cinnamon increased the bioavailability of Pioglitzone (antidiabetic drug).
• Side Effects
  • Oral lesions were shown to be associated with the use of oral cinnamon products like herbal toothpaste and chewing gum.
  • Occupational allergy has been reported with use of cinnamon (due to exposure to its compounds).
  • Use of vaginal suppositories containing cinnamon oil resulted in allergic contact dermatitis.
  • Generalized systemic dermatitis after consuming herbal tea that contained large amounts of cinnamon.

  A systematic review of adverse effects reported that gastrointestinal disorders and allergic reactions were most frequent after consuming cinnamon, but self-limiting in many cases.

• Scientific Name

  Cinnamomum zeylanicum, Cinnamomum aromaticum, Cinnamomum loureiroi, Cinnamomum burmannii

• Clinical Summary

  Cinnamon refers to several plants that belong to the genus Cinnamomum, native to Southeast Asia. The bark, rich in essential oil, is used as a flavoring agent and as a spice. Medicinal uses include appetite stimulation, treatment of arthritis, inflammation, and dyspepsia. In traditional Chinese medicine, cinnamon is used along with other herbs in decoctions to treat colds. In vitro studies have demonstrated that cinnamon has antioxidant ^(1) (2), anti-inflammatory ⁽³⁾, immunomodulatory ^(4) (5), antimicrobial ⁽⁶⁾, antitumor ⁽⁷⁾ , and antiestrogenic ⁽²⁶⁾ properties.

  Cinnamon has been studied in clinical trials for type 2 diabetes but results are conflicting ^{(8) (9) (10) (11) (37)}. However, conclusions of a meta analysis and a review suggest improvements in glycemic control with cinnamon and its extracts in patients with type 2 diabetes ^(12) (36).  According to another meta analysis, supplementation also affected significant reductions in blood triglycerides and total cholesterol concentrations ⁽³⁸⁾. Additional studies reported benefits of cinnamon extracts in decreasing insulin resistance in women with polycystic ovary syndrome (POCS) ⁽³⁹⁾; in improving metabolic syndrome ⁽⁴⁰⁾; for reducing dental plaque and gingivitis in healthy adults ⁽³²⁾; and topical use of a cinnamon ointment alleviated perineal pain and improved healing of episiotomy incision in postpartum women ⁽³³⁾.

  Certain cinnamon products are high in coumarin ^(18) (17) content that can cause hepatotoxicity ⁽¹⁹⁾ and can also interact with other prescription drugs ⁽²⁰⁾.

• Food Sources

  Cinnamon bark

• Purported Uses
  • Diabetes
  • Stomach ulcers
  • Gingivitis
  • Inflammation
  • Arthritis
• Mechanism of Action

  Hydroxycinnamaldehyde, a compound present in cinnamon, exerts anti-inflammatory effects by inhibiting nitric oxide production by inhibiting nuclear factor (NF)-kappaB ⁽³⁾. Cinnamon also inhibits hepatic HMG-CoA reductase activity ⁽²⁴⁾ and reduces the level of blood lipids in animals and humans ⁽¹⁰⁾. In another study, methylhydroxychalcone polymer, isolated from cinnamon, was shown to mimic insulin by activating the insulin receptors ⁽²³⁾.

  Cinnamon extract binds to estrogen-receptor beta and has a direct stimulatory effect on bone formation ⁽²⁵⁾. The n-hexane extract of cinnamon has antiestrogenic activity ⁽²⁶⁾. In other studies, cinnamon extract was shown to inhibit nuclear factor (NF) kappaB and AP1 leading to apoptosis ⁽⁷⁾. It also showed antiangiogenic effects by inhibiting the vascular endothelial growth factor (VEGF) ⁽²²⁾.

• Adverse Reactions
  • Plasma cell gingivitis (PCG) and stomatitis: Following use of oral cinnamon products including toothpaste and chewing gum ^{(13) (15) (16) (27) (34)}
  • Occupational allergy in a baker: Due to exposure to cinnamal, a compound in cinnamon ⁽²⁸⁾
  • Allergic contact dermatits: In an 18-year-old following use of vaginal suppositories containing cinnamon oil ⁽²⁹⁾
  • Generalized systemic dermatitis: In a 26-year old after drinking several cups of herbal tea containing large amounts of cinnamon ⁽⁴¹⁾

  A systematic review of adverse effects reported that gastrointestinal disorders and allergic reactions were most frequent after consuming cinnamon, but self-limiting in many cases ⁽⁴²⁾.

• Herb-Drug Interactions
  • Cytochrome P450 substrates: Cinnamon inhibits cytochrome P450 2C9 and 3A4 (31), 2A6 ⁽⁴³⁾, 2D ⁽⁴⁴⁾, and may interfere with the actions of drugs metabolized by these enzyme ⁽³¹⁾.
  • Statins: When taken along with statins, cinnamon has been reported to cause hepatitis ⁽³⁵⁾.
  • Pioglitazone: Cinnamon enhanced bioavailability upon concomitant use ⁽⁴⁵⁾.
• Herb Lab Interactions
  • Cinnamon may lower blood glucose and cholesterol levels but the evidence is mixed ^(8) (10).
  • Theoretically, cinnamon may increase prothrombin time ⁽³⁰⁾.
• References

  1. Kim SH, Hyun SH, Choung SY. Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice. Biofactors. 2006;26(3):209-219.

  2. Lin CC, Wu SJ, Chang CH, et al. Antioxidant activity of Cinnamomum cassia. Phytother Res. Aug 2003;17(7):726-730.

  3. Lee SH, Lee SY, Son DJ, et al. Inhibitory effect of 2’-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-kappa B activation in RAW 264.7 cells. Biochem Pharmacol. Mar 1 2005;69(5):791-799.

  4. Reddy AM, Seo JH, Ryu SY, et al. Cinnamaldehyde and 2-methoxycinnamaldehyde as NF-kappaB inhibitors from Cinnamomum cassia. Planta Med. Sep 2004;70(9):823-827.

  5. Koh WS, Yoon SY, Kwon BM, et al. Cinnamaldehyde inhibits lymphocyte proliferation and modulates T-cell differentiation. Int J Immunopharmacol. Nov 1998;20(11):643-660.

  6. Shahverdi AR, Monsef-Esfahani HR, Tavasoli F, et al. Trans-cinnamaldehyde from Cinnamomum zeylanicum bark essential oil reduces the clindamycin resistance of Clostridium difficile in vitro. J Food Sci. Jan 2007;72(1):S055-058.

  7. Kwon HK, Hwang JS, So JS, et al. Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1. BMC Cancer. 2010;10:392.

  8. Blevins SM, Leyva MJ, Brown J, et al. Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes. Diabetes Care. Sep 2007;30(9):2236-2237.

  9. Khan A, Safdar M, Ali Khan MM, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. Dec 2003;26(12):3215-3218.

  10. Mang B, Wolters M, Schmitt B, et al. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest. May 2006;36(5):340-344.

  11. Vanschoonbeek K, Thomassen BJ, Senden JM, et al. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. J Nutr. Apr 2006;136(4):977-980.

  12. Davis PA, Yokoyama W. Cinnamon intake lowers fasting blood glucose: meta-analysis. J Med Food. Sep 2011;14(9):884-889.

  13. Anil S. Plasma cell gingivitis among herbal toothpaste users: a report of three cases. J Contemp Dent Pract. 2007;8(4):60-66.

  14. Endo H, Rees TD. Clinical features of cinnamon-induced contact stomatitis. Compend Contin Educ Dent. Jul 2006;27(7):403-409; quiz 410, 421.

  15. Endo H, Rees TD. Cinnamon products as a possible etiologic factor in orofacial granulomatosis. Med Oral Patol Oral Cir Bucal. Oct 2007;12(6):E440-444.

  16. Kind F, Scherer K, Bircher AJ. Allergic contact stomatitis to cinnamon in chewing gum mistaken as facial angioedema. Allergy. Feb 2010;65(2):276-277.

  17. Lungarini S, Aureli F, Coni E. Coumarin and cinnamaldehyde in cinnamon marketed in Italy: a natural chemical hazard? Food Addit Contam Part A Chem Anal Control Expo Risk Assess. Nov 2008;25(11):1297-1305.

  18. Woehrlin F, Fry H, Abraham K, et al. Quantification of flavoring constituents in cinnamon: high variation of coumarin in cassia bark from the German retail market and in authentic samples from indonesia. J Agric Food Chem. Oct 13 2010;58(19):10568-10575.

  19. Abraham K, Wohrlin F, Lindtner O, et al. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res. Feb 2010;54(2):228-239.

  20. Federal Institute for Risk Assessment. Selected Questions about coumarin in cinnamon and other foods. http://www.bfr.bund.de/cd/8487. Accessed October 10, 2018.

  21. Dugoua JJ, Seely D, Perri D, et al. From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark. Can J Physiol Pharmacol. Sep 2007;85(9):837-847.

  22. Lu J, Zhang K, Nam S, et al. Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling. Carcinogenesis. Mar 2010;31(3):481-488.

  23. Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr. Aug 2001;20(4):327-336.

  24. Lee JS, Jeon SM, Park EM, et al. Cinnamate supplementation enhances hepatic lipid metabolism and antioxidant defense systems in high cholesterol-fed rats. J Med Food. Fall 2003;6(3):183-191.

  25. Lee KH, Choi EM. Stimulatory effects of extract prepared from the bark of Cinnamomum cassia blume on the function of osteoblastic MC3T3-E1 cells. Phytother Res. Nov 2006;20(11):952-960.

  26. Kim IG, Kang SC, Kim KC, et al. Screening of estrogenic and antiestrogenic activities from medicinal plants. Environ Toxicol Pharmacol. Jan 2008;25(1):75-82.

  27. Siqueira AS, Santos CC, Cristino MR, et al. Intraoral contact mucositis induced by cinnamon-flavored chewing gum—a case report. Quintessence Int. Oct 2009;40(9):719-721.

  28. Guarneri F. Occupational allergy to cinnamal in a baker. Contact Dermatitis. Nov 2010;63(5):294.

  29. Lauriola MM, De Bitonto A, Sena P. Allergic contact dermatitis due to cinnamon oil in galenic vaginal suppositories. Acta Derm Venereol. Mar 2010;90(2):187-188.

  30. Chase CK, McQueen CE. Cinnamon in diabetes mellitus. Am J Health Syst Pharm. May 15 2007;64(10):1033-1035.

  31. Kimura Y, Ito H, Hatano T. Effects of mace and nutmeg on human cytochrome P450 3A4 and 2C9 activity. Biol Pharm Bull. 2010;33(12):1977-82.

  32. Gupta D, Jain A. Effect of Cinnamon Extract and Chlorhexidine Gluconate (0.2%) on the Clinical Level of Dental Plaque and Gingival Health: A 4-Week, Triple-Blind Randomized Controlled Trial. J Int Acad Periodontol. 2015 Jul;17(3):91-8.

  33. Mohammadi A, Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Javadzadeh Y, Fardiazar Z, Effati-Daryani F. Effects of cinnamon on perineal pain and healing of episiotomy: a randomized placebo-controlled trial. J Integr Med. 2014 Jul;12(4):359-66.

  34. Calapai G, Miroddi M, Mannucci C, Minciullo P, Gangemi S. Oral adverse reactions due to cinnamon-flavoured chewing gums consumption. Oral Dis. 2014 Oct;20(7):637-43.

  35. Brancheau D, Patel B, Zughaib M. Do cinnamon supplements cause acute hepatitis? Am J Case Rep. 2015 Apr 29;16:250-4.

  36. Costello RB, Dwyer JT, Saldanha L, Bailey RL, Merkel J, Wambogo E. Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes? A Narrative Review. J Acad Nutr Diet. 2016 Nov;116(11):1794-1802.

  37. Zare R, Nadjarzadeh A, Zarshenas MM, Shams M, Heydari M. Efficacy of cinnamon in patients with type II diabetes mellitus: A randomized controlled clinical trial. Clin Nutr. 2018 Mar 11. pii: S0261-5614(18)30114-6.

  38. Maierean SM, Serban MC, Sahebkar A, et al. The effects of cinnamon supplementation on blood lipid concentrations: A systematic review and meta-analysis. J Clin Lipidol. 2017 Nov – Dec;11(6):1393-1406.

  39. Hajimonfarednejad M, Nimrouzi M, Heydari M, Zarshenas MM, Raee MJ, Jahromi BN. Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial. Phytother Res. 2018 Feb;32(2):276-283.

  40. Gupta Jain S, Puri S, Misra A, Gulati S, Mani K. Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial. Lipids Health Dis. 2017 Jun 12;16(1):113.

  41. Mertens M, Gilissen L, Goossens A, Lambert J, Vermander E, Aerts O. Generalized systemic allergic dermatitis caused by Cinnamomum zeylanicum in a herbal tea. Contact Dermatitis. 2017 Oct;77(4):259-261.

  42. Hajimonfarednejad M, Ostovar M, Raee MJ, Hashempur MH, Mayer JG, Heydari M. Cinnamon: A systematic review of adverse events. Clin Nutr. 2018 Apr 5. pii: S0261-5614(18)30125-0.

  43. Chan J, Oshiro T, Thomas S, et al. Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. Drug Metab Dispos. 2016 Apr;44(4):534-43.

  44. Taheri A, Lavasani H, Kasirzadeh S, Sheikholeslami B, Ardakani YH, Rouini MR. Changes in CYP2D enzyme activity following induction of type 2 diabetes, and administration of cinnamon and metformin: an experimental animal study.Xenobiotica. 2018 Oct;48(10):984-989.

  45. Mamindla S, Koganti VSRGP, Ravouru N, Koganti B. Effect of Cinnamomum cassia on the Pharmacokinetics and Pharmacodynamics of Pioglitazone. Curr Clin Pharmacol. 2017;12(1):41-49.