The EFSA Journal (2006) 391a,b,c,d, 1-6

The EFSA Journal (2006) 391a,b,c,d, 1-6 Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to Calcium, Magnesium and Zinc Malate added for nutritional purposes to food supplements as sources for Calcium, Magnesium and Zinc and to Calcium Malate added for nutritional purposes to foods for particular nutritional uses and foods intended for the general population as source for Calcium Question n EFSA-Q-2005-134, 145, 159 and Q-2006-140 Adopted on 27 September 2006 SUMMARY The present opinion only deals with the safety and bioavailability of particular sources of calcium, magnesium and zinc, calcium, magnesium and zinc malates to be used in food supplements and in foods for particular nutritional uses and in foods intended for the general population. The safety of calcium, magnesium and zinc, in terms of the amounts that may be consumed, is outside the remit of this Panel. The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) has been asked to advice on the safety and bioavailability of magnesium and zinc malate for use in food supplements and calcium malate for use in food supplements, foods for particular nutritional uses and foods intended for the general population. As malates of calcium, magnesium and zinc dissociate in the gastrointestinal tract, the Panel concluded that the bioavailability of calcium, magnesium and zinc from malates is expected to be similar to the bioavailability from other dissociable calcium, magnesium and zinc salts permitted to be used in food and food supplements. On the basis of the data used to establish the existing ADI of DL-malic acid (JECFA, 1986), the Panel also concluded that the use of malates as sources for calcium, magnesium and zinc in food supplements and as source of calcium in foods for particular nutritional uses and foods intended for the general population is of no safety concern. In foods prepared for infants and young children, however, only L-malates should be used according to the previous opinion of the SCF (1992). http://www.efsa.eu.int/science/afc/afc_opinions/catindex_en.html

Malates in food supplements The EFSA Journal (2006) 391 a,b,c,d, p. 2 of 6 KEY WORDS Calcium malate, magnesium malate, zinc malate, malic acid, food supplements, foods for particular nutritional uses, foods intended for the general population. BACKGROUND The European Community legislation lists nutritional substances that may be used for nutritional purposes in certain categories of foods as sources of certain nutrients. The Commission has received requests for the evaluation of calcium, magnesium and zinc malate added for nutritional purposes to food supplements and of calcium malate added for nutritional purposes in foods for particular nutritional uses and foods intended for the general population. The relevant Community legislative measures are: Directive 2002/46/EC of the European Parliament and of the Council on the approximation of the laws of the Member States relating to food supplements (EC, 2002). Commission Directive 2001/15/EC on substances that may be added for specific nutritional purposes in foods for particular nutrition (EC, 2001). In addition, there is a Commission proposal for a regulation on the addition of vitamins and minerals and certain other substances to foods (EC, 2003). TERMS OF REFERENCE In accordance with Article 29 (1) (a) of Regulation (EC) No 178/2002, the European Commission asks the European Food Safety Authority to provide scientific opinions, based on its consideration of the safety and bioavailability of calcium, magnesium and zinc malate added for nutritional purposes to food supplements and of calcium malate added for nutritional purposes in foods for particular nutritional uses and foods intended for the general population. ASSESSMENT Chemistry Calcium, magnesium and zinc malate are salts of malic acid with the chemical formula CaC 4 H 4 O 5, MgC 4 H 4 O 5 and ZnC 4 H 4 O 5 and the CAS Registration Numbers 17482-42-7, 869-06-7 and 2847-05-4, respectively. Information on the chirality of calcium and zinc malate has not been provided. Only the magnesium salt was specified as magnesium DL-malate trihydrate.

Malates in food supplements The EFSA Journal (2006) 391 a,b,c,d, p. 3 of 6 Specifications According to the petitioners, calcium and magnesium malate are not less than 97.5% pure and zinc malate not less than 97% pure on anhydrous basis. The proposed specifications of calcium and magnesium malate comply with the specifications of calcium malate and malic acid for use as food additives in Directive 96/77/EC. In the case of zinc malate, maximum levels for malic acid, fumaric acid and cadmium are not given. Exposure According to the petitioners, the quantity of calcium, magnesium and zinc malate to be added to food supplements will be determined by individual formulators, but is normally the quantity necessary to supply adults with up to 2400 mg calcium/day, 250 mg magnesium/day and 15 mg zinc/day, respectively. The maximum total intakes of calcium and zinc from supplements, food, and water were estimated by the petitioner to be 4500 and 77 mg/day, respectively. Based on a potential intake of 2400 mg calcium/day from calcium malate in food supplements as indicated by the petitioners, the equivalent intake of malic acid would be around 8000 mg/day. The intake of malic acid equivalent to 250 mg magnesium/day and 15 mg zinc/day from supplements would be around1400 and 30 mg/day, respectively. In comparison, the daily human consumption of malic acid from its natural occurence in vegetables, fruits and their juices was estimated to be in the order of 1500 to 3000 mg/day (Hartmann and Hillig, 1934). Although this reference is old it is in accordance with data on malic acid in fruits in the range up to 1990 mg/100 g (Souci et al., 2000). Taking into account the maximum levels of malic acid resulting from current good manufacturing practice of e.g. 3.4% for non-alcoholic beverages and 3.5% for processed fruits and fruit juices (FDA, 2003), the intake of malic acid from its use as food additive is likely to be higher than from processed fruits and fruit juices. The Panel notes that malic acid is authorised as a food additive in all foods to quantum satis. Existing authorisations and evaluations DL-malic acid as well as sodium, potassium and calcium malate are permitted food additives with the numbers E296, E350, E351 and E352i, respectively. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) evaluated malic acid and derived on the basis of its well-established metabolic pathway and the daily consumption of malic acid-containing food a group ADI not specified for DL-malic acid and sodium, potassium and calcium DL-malate (JECFA, 1980; JECFA, 1986). The EC Scientific Committee on Food (SCF) agreed with this group ADI (SCF, 1990), but considered only the L-isomer acceptable for use in foods prepared for infants and young children (SCF, 1992). For calcium, magnesium and zinc, the following Tolerable Upper Intake Levels have been established by the SCF: 2500 mg calcium/day for adults from all sources (SCF,

Malates in food supplements The EFSA Journal (2006) 391 a,b,c,d, p. 4 of 6 2003a), 250 mg magnesium/day for readily dissociable magnesium salts and compounds like magnesium oxide not including magnesium normally present in foods and beverages for adults and children from 4 years on (SCF, 2001), and 25 mg zinc/day for adults from all sources (SCF, 2003b). Biological and toxicological data Bioavailability of calcium, magnesium and zinc from their malates Studies on the bioavailability of calcium, magnesium and zinc from their malates in comparison to the commonly used sources for these minerals have not been submitted. Toxicological data The toxicological evaluation is based on the toxicological data on malic acid reviewed by JECFA (1966) and the Cosmetic Ingredient Review Expert Panel (2001) and the data on calcium, magnesium and zinc reviewed by the SCF (2001, 2003a, 2003b). DISCUSSION It can be expected that calcium, magnesium and zinc malate will easily dissolve and dissociate in the gastrointestinal tract and that their cations will be absorbed separately from the malate anion. Therefore, the bioavailability from calcium, magnesium and zinc from malates will likely be in the same range as the bioavailability from other dissociable salts of these minerals. The intake of calcium, magnesium and zinc from malates used in food supplements was estimated by the petitioners to be slightly below or equal to the Tolerable Upper Intake Levels of these cations established by the SCF (2001, 2003a, 2003b). The Panel notes that there are also other sources of calcium, magnesium and zinc that contribute to the total intakes. The intake of malic acid from the use of calcium malate in supplements is relatively high but the well understood metabolism of malic acid and its role in the citric acid cycle does not give rise to any concern. CONCLUSION The present opinion only deals with the safety and bioavailability of particular sources of calcium, magnesium and zinc, calcium, magnesium and zinc malates, to be used in food supplements and in foods for particular nutritional uses and in foods intended for the general population. The safety of calcium, magnesium and zinc, in terms of the amounts that may be consumed, is outside the remit of this Panel.

Malates in food supplements The EFSA Journal (2006) 391 a,b,c,d, p. 5 of 6 The Panel concludes that the bioavailability of calcium, magnesium and zinc from malates is expected to be similar to the bioavailability from other dissociable calcium, magnesium and zinc salts permitted to be used for food supplements. The safety evaluation of the malates was based on the data used to establish the existing ADI of DL-malic acid (JECFA, 1986). On this basis, the Panel concluded that the use of calcium, magnesium and zinc malate as sources for calcium, magnesium and zinc in food supplements and of calcium malate in foods for particular nutritional uses and foods intended for the general population as source for calcium is of no safety concern. In foods prepared for infants and young children, however, only L-malates should be used according to the previous opinion of the SCF (1992). DOCUMENTATION PROVIDED TO EFSA Dossier on Calcium Malate. Submitted by Health Food Manufacturers Association, UK (June, 2005). Dossier on Calcium Malate. Application for derogation submitted by Sami Labs Limited, Bangalore, India (July, 2005). Dossier on Magnesium Malate submitted by Health Food Manufacturers Association, UK (May, 2005). Dossier on Zinc Malate. Submitted by Health Food Manufacturers Association, UK (May, 2005). REFERENCES Cosmetic Ingredient Review Expert Panel (2001). Final report on the safety assessment of malic acid and sodium malate. Internat. J. Toxicol. 2O (Suppl.1), 47-55. EC (2001). Commission Directive 2001/15/EC of 15 February 2001 on substances that may be added for specific nutritional purposes in foods for particular nutritional uses. Official Journal of the European Communities, L52, 22.2.2001, pg 19-25. http://europa.eu.int/eur-lex/en/consleg/pdf/2001/en_2001l0015_do_001.pdf EC (2002) Directive 2002/46/EC of the European Parliament and of the Council on the approximation of the laws of the Member States relating to food supplements. Official Journal of the European Communities, L183, 12.7.2002, pg 51-58 http://eurlex.europa.eu/lexuriserv/site/en/oj/2002/l_183/l_18320020712en00510057.pdf EC (2003) Commission proposal for a regulation on the addition of vitamin and minerals and certain other substances to foods - COM (2003) 671 final

Malates in food supplements The EFSA Journal (2006) 391 a,b,c,d, p. 6 of 6 European Pharmacopoeia (2005). www.pheur.org FDA (2003). Fed. Reg. 184.1069. 21 CFR Ch. I (4-1-03). Hartmann B.G. and Hillig F. (1934). J. Ass. Off. Agric. Chem. 17(3), 522, quoted by JECFA (1966). JECFA (1966). Toxicological evaluation of some antimicrobials, antioxidants, emulsifiers, stabilizers, flour-treatment agents, acids and bases. FAO Nutrition Meetings Report Series No. 40A,B,C. WHO/Food Add./67.29 http://www.inchem.org/documents/jecfa/jecmono/40abcj01.htm JECFA (1980). Evaluation of certain food additives. WHO Technical Report Series 648. http://whqlibdoc.who.int/trs/who_trs_648.pdf JECFA (1986). Evaluation of certain food additives and contaminants. WHO Technical Report Series 733. http://whqlibdoc.who.int/trs/who_trs_733.pdf SCF (1990). First series of food additives of various technological functions (Opinion expressed on 18 May 1990). Reports of the Scientific Committee for Food (Twentyfifth series). http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_25.pdf SCF (1992). Minutes of the 86th meeting of the Scientific Committee for Food held on 8-9 October 1992. SCF (2001). Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Magnesium (expressed on 26 September 2001). http://ec.europa.eu/food/fs/sc/scf/out105_en.pdf SCF (2003a). Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Zinc (expressed on 5 March 2003). http://ec.europa.eu/food/fs/sc/scf/out177_en.pdf SCF (2003b). Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Calcium (expressed on 4 April 2003). http://ec.europa.eu/food/fs/sc/scf/out194_en.pdf Souci S. W., Fachmann W. and Kraut H. (2000). Food Composition and Nutrition Tables. Wiss. Verlagsgesellsch. Stuttgart. SCIENTIFIC PANEL MEMBERS F. Aguilar, H. Autrup, S. Barlow, L. Castle, R. Crebelli, W. Dekant, K.-H. Engel, N. Gontard, D. Gott, S. Grilli, R. Gürtler, J.-C. Larsen, C. Leclercq, J.-C. Leblanc, F. X. Malcata, W. Mennes, M.-R. Milana, I. Pratt, I. Rietjens, P. Tobback, F. Toldrá.