Coumarin and Cinnamaldehyde in Cinnamon Marketed in Italy: a Natural Chemical Hazard? Silvia Lungarini, Federica Aureli, Ettore Coni To cite this version: Silvia Lungarini, Federica Aureli, Ettore Coni. Coumarin and Cinnamaldehyde in Cinnamon Marketed in Italy: a Natural Chemical Hazard?. Food Additives and Contaminants, 2008, 25 (11), pp.1297-1305. 10.1080/02652030802105274. hal-00577395 HAL Id: hal-00577395 https://hal.archives-ouvertes.fr/hal-00577395 Submitted on 17 Mar 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Food Additives and Contaminants For Peer Review Only Coumarin and Cinnamaldehyde in Cinnamon Marketed in Italy: a Natural Chemical Hazard? Journal: Food Additives and Contaminants Manuscript ID: TFAC-2008-011.R1 Manuscript Type: Original Research Paper Date Submitted by the 01-Apr-2008 Author: Complete List of Authors: Lungarini, Silvia; Istituto Superiore di Sanità, National Centre for Food Quality and Risk Assessment Aureli, Federica; Istituto Superiore di Sanità, National Centre for Food Quality and Risk Assessment Coni, Ettore; Istituto Superiore di Sanità, National Centre for Food Quality and Risk Assessment Methods/Techniques: Clean-up, Exposure assessment, HPLC, Method validation Additives/Contaminants: Flavourings, Natural toxicants Food Types: Bakery products, Beverages, Biscuits, Confectionary http://mc.manuscriptcentral.com/tfac Email: [email protected] Page 1 of 23 Food Additives and Contaminants 1 2 Coumarin and cinnamaldehyde in cinnamon marketed in Italy: a natural 3 4 5 chemical hazard? 6 7 8 9 10 SILVIA LUNGARINI, FEDERICA AURELI and ETTORE CONI 11 12 13 14 15 National Centre on Food Quality and Risk Assessment, 16 For Peer Review Only 17 Istituto Superiore di Sanità, Viale Regina Elena 299, 18 19 00161 Rome, Italy 20 21 22 23 24 25 26 27 Correspondence: Ettore Coni. E-mail: [email protected] 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 http://mc.manuscriptcentral.com/tfac Email: [email protected] Food Additives and Contaminants Page 2 of 23 1 2 Abstract 3 4 Some plants that are processed into foods often contain natural substances that may be hazardous to 5 6 7 human health. One example is coumarin that is known to cause liver and kidney damage in rats, 8 9 mice and probably in humans. The main source of coumarin in the diet is cinnamon. The name 10 11 12 cinnamon is correctly used to refer to Ceylon Cinnamon, also known as “true cinnamon”. However, 13 14 other plant species are sometimes sold with the label of cinnamon. This is the case of Cinnamomun 15 16 aromaticum (Cassia).For In recent Peer years, due Reviewto its cheaper price, CassOnlyia is replacing true cinnamon in 17 18 19 the European food market being largely used in the preparation of some kinds of sweets. Several 20 21 European health agencies have recently warned against consuming high amounts of Cassia, due to 22 23 its high content of coumarin. In this study, thirty-four samples of cinnamon and fifty samples of 24 25 26 cinnamon-containing foodstuffs were collected from the Italian market. Quantitative determinations 27 28 of coumarin and cinnamaldehyde were performed by HPLC with diode array detector (DAD). The 29 30 analytical method was in house validated assessing recovery, repeatability, linearity, LOD and 31 32 33 LOQ. The results showed that about 51 % of cinnamon samples consisted of Cassia, 10 % were 34 35 probably a blend of cassia and Ceylon cinnamon whereas only 39 % were actually Ceylon 36 37 38 cinnamon. As far as cinnamon-containing foods are concerned, the samples often exceeded the 39 -1 40 maximum level fixed in the European Flavourings Directive of 2 mg kg . 41 42 43 44 45 46 47 Keywords: Coumarin; cinnamaldehyde, cinnamon; high-performance liquid chromatography. 48 49 50 51 52 53 54 55 56 57 58 59 60 2 http://mc.manuscriptcentral.com/tfac Email: [email protected] Page 3 of 23 Food Additives and Contaminants 1 2 Introduction 3 4 High dietary consumption of fruit and vegetables is promoted by nutritionist because this is 5 6 7 considered healthy. This notwithstanding, some foods of vegetable origin can contain natural 8 9 compounds that are hazardous to human health. One recognized example is coumarin, a natural 10 11 12 occurring flavouring substance which is found in relatively high concentrations in a wide variety of 13 14 plants (Hoult and Paya, 1996). Coumarin was first isolated from Tonka beans, and is present at high 15 16 levels in some essentialFor oils, Peer specifically cassiaReview leaf oil, cinnamon Only leaf and bark oils, lavender oil 17 18 19 and peppermint oil. Coumarin is also found in fruits, green tea and other vegetables, such as 20 21 chicory. However, the main contribution of coumarin in human diet is surely given by cinnamon. 22 23 24 25 26 Besides pepper and vanilla, cinnamon is, in fact, the best-known and most commonly used spice in 27 28 the world. The name cinnamon is correctly used to refer to Ceylon Cinnamon, also known as “true 29 30 cinnamon” (from the botanical name Cinnamomum verum ). In spite of this, other species of the 31 32 33 same genus are sometimes sold with the label of cinnamon. This is the case of Cinnamomun 34 35 aromaticum (Cassia) and Cinnamomum burmanii . The greater part of the spice sold as cinnamon 36 37 38 in the United States and Canada (where true cinnamon is still generally unknown) is actually cassia. 39 40 In some cases, cassia is labelled "Chinese cinnamon" to distinguish it from the more expensive true 41 42 cinnamon, which is the favourite form used in Mexico and Europe. "Indonesian cinnamon" can also 43 44 45 refer to Cinnamomum burmanii , which is also commonly sold in the United States, simply labelled 46 47 as cinnamon. 48 49 50 51 52 In recent years, due to its cheap price, Cassia is replacing true cinnamon also in European food 53 54 market being largely used in the preparation of some kinds of desserts, biscuits, cakes, chocolate, 55 56 57 spicy confectionery, tea, hot cocoa and liqueurs. This considered, the German Federal Institute for 58 59 Risk Assessment (BfR 2006) has recently warned against consuming high amounts of cassia, due to 60 3 http://mc.manuscriptcentral.com/tfac Email: [email protected] Food Additives and Contaminants Page 4 of 23 1 2 its high content of coumarin which is present at much lower concentrations in Cinnamomum verum 3 4 and in Cinnamomum burnanii . 5 6 7 8 9 Coumarin is known to cause liver and kidney damage in rats and mice and there are isolated 10 11 12 incidents of similar hepatotoxicity in humans (WHO 1995). In particular, coumarin is a clear 13 14 carcinogen in rats and possibly in mice for oral exposure, noting that adenomas and carcinomas of 15 16 the liver and bile Forducts and Peerkidney adenomas Review have been observed Only in rats whereas adenomas and 17 18 19 carcinomas of the lung and liver adenomas in mice. 20 21 22 23 Cytochrome P450 (CYP)2A6 is the major enzyme involved in metabolizing coumarin to 7- 24 25 26 hydroxycoumarin. A reduction in CYP2A6 activity will lead to shunting of coumarin into other 27 28 metabolic pathways. In particular, coumarin is metabolized by CYP3A4 to form 3- 29 30 hydroxycoumarin, the major metabolite in mice and rats. It has been seen that an increase in the 3- 31 32 33 hydroxycoumarin ratio is associated with an increased production of the significant cytotoxic 34 35 product o-hydroxyphenylacetylacetaldehyde (O-HPA), suggesting that a shunting of coumarin 36 37 38 metabolism away from 7-hydroxylation is the most important cause of toxicity. Poor CYP2A6 39 40 metabolizers are, thus, more likely to metabolize coumarin via the cytotoxic pathway. Since its 41 42 toxicity, the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in 43 44 45 Contact with Food of European Food Safety Authority (EFSA) has recently established a tolerable 46 47 daily intake (TDI) for coumarin of 0 – 0.1 mg kg -1 bw based on the no-observed-adverse-effect- 48 49 level (NOAEL) for epatotoxicity (EFSA 2004). 50 51 52 53 54 On the other hand, the Directive 88/388/EEC lays down maximum levels for coumarin in foodstuffs 55 56 -1 57 (EEC 1998). In particular, the amount of coumarin is limited to 2 mg kg for foodstuffs and 58 59 beverages with the exception of alcoholic beverages, certain types of caramels and chewing gums 60 (10, 10 and 50 mg kg -1, respectively). The European Commission did not maintain these levels in a 4 http://mc.manuscriptcentral.com/tfac Email: [email protected] Page 5 of 23 Food Additives and Contaminants 1 2 proposed new Regulation but a recent communication from the Commission to the European 3 4 Parliament has reconsidered the coumarin issue owing to new analytical data from BfR (EC 2008). 5 6 7 Germany requested re-introduction of maximum levels and the other Member States agreed with 8 9 this re-introduction.