Scientific Opinion on the re-evaluation of anthocyanins (E 163) as a food additive
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)
Search for more papers by this authorEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)
Search for more papers by this authorAbstract
Following a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to provide a scientific opinion re-evaluating the safety of anthocyanins (E 163). The Panel concluded that the currently available toxicological database was inadequate to establish a numerical ADI for anthocyanins. For anthocyanins extracted from edible fruits and vegetables by aqueous processes, changes in composition would not be expected. The Panel concluded that provided exposure from use as a food additive was comparable to that from the diet the underlying conclusion in the 1975 SCF opinion that such food additives derived from natural sources would still apply. The majority of data are on aqueous grape skin extract (GSKE) and blackcurrant extracts and the Panel considers that exposures estimated from current uses and use levels these extracts are unlikely to be of safety concern. The Panel recommends that the specifications for E 163 should be modified to reflect this conclusion. For anthocyanins extracted from other sources and/or using non-aqueous extraction methods the absence of characterisation does not allow verification that this conclusion in the 1975 SCF opinion could be applied. The Panel noted that for some extracts it had proven possible to assess a group based on toxicological and compositional data on representative samples across the range of extracts. The Panel concluded that refined exposure estimates of anthocyanins used as a food additive were higher than dietary intakes and that these did not include intakes from colouring foods. Therefore the Panel would recommend that appropriate characterisation and toxicological data should be required to permit a further re-evaluation of anthocyanins including comparative data on anthocyanins (E 163) produced by aqueous extraction.
References
- Abraham SK, Schupp N, Schmid U and Stopper H, 2007. Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid. Molecular Nutrition & Food Research, 51, 880–7.
- Aiub C, Stankevicins L, da Costa V, Ferreire F, Mazzei J, Ribeiro da Silva A, Soares de Moura R and Felzenswalb I, 2004. Genotoxic evaluation of a vinifera skin extracts that present pharmacological activities. Food and Chemical Toxicology, 42, 969–73.
- Bentivegna SS and Whitney KM, 2002. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. Food and Chemical Toxicology, 40, 1731–1743.
- Brown JP and Dietrich PS, 1979. Mutagenicity of plant flavonols in the Salmonella/mammalian microsome test: activation of flavonol glycosides by mixed glycosidases from rat cecal bacteria and other sources. Mutation Research 66, 223–240 (as referred to by JECFA, 1982 and TemaNord, 2002).
- Bub A, Watzl B, Heeb D, Rechkemmer G and Briviba K, 2001. Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. European Journal of Nutrition, 40, 113–120.
- Cao G, Muccitelli HU, Sánchez-Moreno C and Prior RL, 2001. Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study. American Journal of Clinical Nutrition. 73, 920–6.
- Carkeet C, Clevidence BA and Novotny JA, 2008. Anthocyanin Excretion by Humans Increases Linearly with Increasing Strawberry Dose. Journal of Nutrition, 138, 897–902.
- Carpenter JA, Wang YP and Powers JJ, 1967. Effects of anthocyanin pigments on certain enzymes. Proc. Soc. Exptl. Biol. Med. 124, 702–706 (as referred to by JECFA, 1982).
- ChemIDplus advanced (via internet, 2008). Accessible via: chem.sis.nlm.nih.gov/chemidplus.
- Clark WG and Mackay EW, 1950. The absorption and excretion of rutin and related flavonoid substances. Journal of American Medical Association, 143, 1411–1415 (as referred to by JECFA, 1982).
- Cox GE and Babish JC, 1978a. Evaluation of the safety of dietary administration of special grape color powder (type BW-AT) on reproduction, lactation and maturation when fed to Sprague-Dawley rats. Unpublished report No. 5417 by Food and Drug Research Laboratories, Inc., submitted to the World Health Organization by FDA (as referred to by JECFA, 1982).
- Cox GE and Babish JC, 1978b. A 90-day feeding study of special grape color powder (type BW-AT) to Beagle dogs. Unpublished report No. 5417 by Food and Drug Research Laboratories, Inc., submitted to the World Health Organization by FDA (as referred to by JECFA, 1982).
- EFSA (European Food Safety Authority), 2007. Guidance of the Scientific Committee on a request from EFSA related to Uncertainties in Dietary Exposure Assessment. The EFSA Journal 2006, 438, 1–54.
- EFSA (European Food Safety Authority), 2008a. Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials on a request from European Commission on Safety of aluminium from dietary intake. The EFSA Journal 2008, 754, 1–34.
- EFSA (European Food Safety Authority), 2008b. Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission on the use of rosemary extracts as a food additive. The EFSA Journal 2008, 721, 1–3.
- EFSA (European Food Safety Authority), 2009. Guidance of the Scientific Committee on Safety assessment of botanicals and botanical preparations intended for use as ingredients in food supplements. EFSA Journal 2009; 7(9): 1249. [19 pp.] doi:10.2093/j.efsa.2009.1249.
- EFSA (European Food Safety Authority), 2011a. Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment. EFSA Journal 2011; 9(3): 2097. [34 pp.] doi:10.2903/j.efsa.2011.2097.
10.2903/j.efsa.2011.2097 Google Scholar
- EFSA (European Food Safety Authority), 2011b. Evaluation of the FoodEx, the food classification system applied to the development of the EFSA Comprehensive European Food Consumption Database. EFSA Journal 2011; 9(3): 1970. [27 pp.] doi:10.2903/j.efsa.2011.1970.
10.2903/j.efsa.2011.1970 Google Scholar
- El Mohsen MA, Marks J, Kuhnle G, Moore K, Debnam E, Srai SK, Rice-Evans C and Spencer JPE, 2006. Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. British Journal of Nutrition, 95, 51–58.
- Erexson GL, 2003. Lack of in vivo clastogenic activity of grape seed and grape skin extracts in a mouse micronucleus assay. Food and Chemical Toxicology, 41, 347–350.
- Felgines C, Texier O, Besson C, Fraisse D, Lamaison JL and Remesy C, 2002. Blackberry anthocyanins are slightly bioavailable in rats. Journal of Nutrition, 132, 1249–53.
- Felgines C, Talavera S, Gonthier MP, Texier O, Scalbert A, Lamaison JL and Remesy C, 2003. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. Journal of Nutrition, 133, 1296–301.
- Felgines C, Talavera S, Texier O, Gil-Izquierdo A, Lamaison JL and Remesy C, 2005. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. Journal of Agricultural and Food Chemistry 53, 7721–7.
- Felgines C, Talavera S, Texier O, Besson C, Fogliano V, Lamaison JL, La Fauci L, Galvano G, Remesy C and Galvano F, 2006. Absorption and metabolism of red orange juice anthocyanins in rats. British Journal of Nutrition 95, 898–904.
- Felgines C, Texier O, Besson C, Lyan B, Lamaison JL and Scalbert A, 2007. Strawberry pelargonidin glycosides are excreted in urine as intact glycosides and glucuronidated pelargonidin derivatives in rats. British Journal of Nutrition, 98, 1126–31.
- Galvez J, Pedro DLCJ, Zarzuelo A and Sanchez DLCF, 1995. Flavonoid inhibition of enzymic and nonenzymic lipid peroxidation in rat liver differs from its influence on the glutathione-related enzymes. Pharmacol. 51, 127–133 (as referred to by TemaNord, 2002).
- Gibb C, Glover V and Sandler M, 1987. In vitro inhibition of phenolsulphotransferase by food and drink constituents. Biochemical Pharmacology, 36, 2325–2330 (as referred to by TemaNord, 2002).
- Griffiths LA and Smith GE, 1972a. Metabolism of myricetin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. 183, 141–151 (as referred to by JECFA, 1982).
- Griffiths LA and Smith GE, 1972b. Metabolism of apigenin and related compounds in the rat. Biochemical Journal, 128, 901–911 (as referred to by JECFA, 1982).
- Habermeyer M, Fritz J, Barthelmes HU, Christensen MO, Larsen MK, Boege F and Marko D, 2005. Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity. Chemical Research in Toxicology 18, 1395–404.
- Harada K, Kano M, Takayanagi T, Yamakawa O and Ishikawa F, 2004. Absorption of acylated anthocyanins in rats and humans after ingesting an extract of Ipomoea batatas purple sweet potato tuber. Bioscience, Biotechnology and Biochemistry, 68, 1500–1507.
- Harrington KE, Robson PJ, Kiely M, Livingstone MB, Lambe J, Gibney MJ. 2001. The North/South Ireland Food Consumption Survey: survey design and methodology. Public Health Nutrition October 4(5A): 1037–42.
- Haveland-Smith RB, 1981. Evaluation of the genotoxicity of some natural food colors using bacterial assays. Mutation Research, 91, 285–290 (as referred to by JECFA, 1982).
- He J, Magnuson BA, Lala G, Tian Q, Schwartz SJ and Giusti MM, 2006. Intact Anthocyanins and Metabolites in Rat Urine and Plasma After 3 Months of Anthocyanin Supplementation. Nutrition and Cancer 54, 3–12.
- Hollands W, Brett GM, Dainty JR, Teucher B and Kroon PA, 2008. Urinary excretion of strawberry anthocyanins is dose dependent for physiological oral doses of fresh fruit. Molecular Nutrition & Food Research. 52, 1097–1105.
- Horwitt KM, 1933. Observations on behavior of the anthocyanin pigment from concord grapes in the animal body. Proceedings of the Society for Experimental Biology and Medicine, 30, 949–951 (as referred to by JECFA, 1982).
- Hubbermann EM, Heins A, Stöckmann H and Schwarz K, 2006. Influence of acids, salts, sugars and hydrocolloids on the colour stability of anthocyanin rich black current and elderberry concentrates. European Food Research and Technology. 223, 83–90.
- Ichiyanagi T, Shida Y, Rahman MM, Hatano Y, Matsumoto H, Hirayama M and Konishi T, 2005. Metabolic Pathway of Cyanidin 3-O-β-D-Glucopyranoside in rats. Journal of Agricultural and Food Chemistry, 53, 145–150.
- Ichiyanagi T, Shida Y, Rahman MM, Hatano Y and Konishi T, 2006. Bioavailability and Tissue Distribution of Anthocyanins in Bilberry (Vaccinium myrtillus L.) Extract in Rats. Journal of Agricultural and Food Chemistry, 54, 6578–6587.
- IUNA 2005. Irish National Childrens Food Survey. Irish Universities Nutrition Alliance. www.iuna.net/?p=27.
- JECFA 26th report, 1982. WHO/FAO Joint Expert Committee on Food Additives. Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Series, No 17.
- JECFA, 2006. Monograph on grape skin extract. Available at: www.fao.org/ag/agn/jecfa-additives/specs/Monograph1/Additive-214.pdf.
- Kay CD, Mazza G, Holub BJ and Wang J, 2004. Anthocyanin metabolites in human urine and serum. British Journal of Nutrition. 91, 933–942.
- Kay CD, Mazza G and Holub BJ, 2005. Anthocyanins Exist in the Circulation Primarily as Metabolites in Adult Men. Journal of Nutrition, 135, 2582–2588.
- Kong JM, Chia LS, Goh NK, Chia TF and Brouillard R, 2003. Analysis and biological activities of anthocyanins. Photochemistry 64, 923–933.
- Kuhnau J, 1976. The flavanoids. A class of semi-essential food components: their role in human nutrition. World Review of Nutrition and Dietetics, 24, 117–191.
- Lapidot T, Harel S, Granit R and Kanner J, 1998. Journal of Agricultural and Food Chemistry 46, 4297–4302.
- Lietti A and Forni G, 1976. Studies on Vaccinium myrtillus anthocyanosides. II. Aspects of anthocyanin pharmacokinetics in the rat. Arzneimittel-Forschung. 26.
- MacGregor JT and Jurd L, 1978. Mutagenicity of plant flavanoids: Structural requirements for mutagenic activity in Salmonella typhimurium. Mutation Research. 54, 297–309 (as referred to by JECFA, 1982).
- Matsumoto H, Inaba H, Kishi M, Tominaga S, Hirayama M and Tsuda T, 2001. Orally Administered Delphinidin 3-Rutinoside and Cyanidin 3-Rutinoside Are Directly Absorbed in Rats and Humans and Appear in the Blood as the Intact Forms. Journal of Agricultural and Food Chemistry, 49, 1546–1551.
- Matsumoto H, Ichiyanagi T, Iida H, Ito K, Tsuda T, Hirayama M and Konishi T, 2006. Ingested Delphinidin-3-rutinoside Is Primarily Excreted to Urine as the Intact Form and to Bile as the Methylated Form in Rats. Journal of Agricultural and Food Chemistry, 54, 578–582.
- Mazza G, Kay CD, Cottrell T and Holub BJ, 2002. Absorption of Anthocyanins from Blueberries and Serum Antioxidant Status in Human Subjects. Journal of Agricultural and Food Chemistry, 50, 7731–7737.
- McGhie TK and Walton MC, 2007. The bioavailability and absorption of anthocyanins: towards a better understanding. Molecular Nutrition & Food Research, 51, 702–13.
- Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P, Pacheco-Palencia LA, Meibohm B, Talcott ST and Derendorf H, 2008. Pharmacokinetics of Anthocyanins and Antioxidant Effects after the Consumption of Anthocyanin-Rich Acai Juice and Pulp (Euterpe oleracea Mart.) in Human Healthy Volunteers. Journal of Agricultural and Food Chemistry, 56 (17), 7796–802.
- Moudgal NR, Raghupathy E and Sarma PS, 1958. Studies on goitrogenic agents in foods. III. Goitrogenic action of some glycosides isolated from edible nuts. Journal of Nutrition, 66, 291–303 (as referred to by JECFA, 1982).
- Nielsen ILF, Rasmussen SE, Mortensen A, Ravn-Hagen G, Ping Ma H, Knuthsen P, Fischer Hansen B, McPhail D, Fresse R, Breinholt V, Frandsen H and Dragsted LO, 2005. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce arherosclerosis in watanabe heritable hyperlipidemeic rabbits. Molecular Nutrition & Food Research, 49, 301–308.
- Nielsen ILF, Dragsted LO, Ravn-Hagen G, Fresse R and Rasmussen SE, 2003. Absorption and excretion of black currant anthocyanins in humans and watanabe hyperlipidemic rabbits. Journal of Agricultural and Food Chemistry, 51, 2813–2820.
- Ohnishi R, Ito H, Kasajima N, Kaneda M, Kariyama R, Kumon H, Hatano T and Yoshida T, 2006. Urinary excretion of anthocyanins in humans after cranberry juice ingestion. Bioscience, Biotechnology and Biochemistry. 70, 1681–1687.
- Parkinson TM and Brown JP, 1981. Metabolic fate of food colorants. Annual Review of Nutrition. 1, 175–205.
- Pourrat H, Bastide P, Dorier P and Tronche P, 1967. Préparation et activité thérapeutique de quelques glycosides d'anthocyanes. Chim. Thérap. 2, 33–38 (as referred to by JECFA, 1982).
- SCF, 1975. Reports of the Scientific Committee for Food (1st series), opinion expressed in 1975, 17–29.
- SCF, 1997. Reports of the Scientific Committee for Food (41st series), opinion expressed in 1997, 1–8.
- Scheline RR, 1968. The metabolism of drugs and other organic compounds by the intestinal microflora. Acta Pharmacologica Et Toxicologica 26, 332–342 (as referred to by JECFA, 1982).
- Scheline RR, 1978. Mammalian metabolism of plant xenobiotics. New York, Academic Press (as referred to by JECFA, 1982).
- Scotter M J and Castle L, 2004. Chemical interactions between additives in foodstuffs: a review. Food Additives and Contaminant, 21(2), 93–124.
- Scotter MJ, 2011. Methods for the determination of European Union-permitted addednatural food additives in foods: a review. Food Additivies and Contaminats: Part A. 1–70.
- Somaatmadja D, Powers JJ and Hamdy MK, 1964. Anthocyanins. VI. Chelation studies on anthocyanins and other related compounds. Journal of Food Science. 29, 655–660 (as referred to by JECFA, 1982).
- Stoner GD, Sardo C, Apseloff G, Mullet D, Wargo W, Pound V, Singh A, Sanders J, Aziz R, Casto B and Sun XL, 2005. Pharmacokinetics of Anthocyanins and Ellagic Acid in Healthy Volunteers Fed Freeze-Dried Black Raspberries Daily for 7 Days. Journal of Clinical Pharmacology, 45, 1153–1164.
- Sweeny JG, Iacobucci GA, Brusick D and Jagannath DR, 1981. Structure-activity relationships in the mutagenicity of quinone methides of 7-hydroxyflavylium salts for Salmonella typhimurium. Mutation Research 82, 275–283 (as referred to by TemaNord, 2002).
- Talavera S, Felgines C, Texier O, Besson C, Lamaison JL and Remesy C, 2003. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. Journal of Nutrition, 133, 4178–82.
- Talavera S, Felgines C, Texie, O, Besson C, Manach C, Lamaison JL and Remesy C, 2004. Anthocyanins are efficiently absorbed from the small intestine in rats. Journal of Nutrition, 134, 2275–9.
- Talavera S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison JL and Remesy C, 2005. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. Journal on Agricultural and Food Chemistry, 53, 3902–8.
- Tennant D, 2007a. Screening potential intakes of natural food colours. Report provided for the Natural Food Colours Association (NATCOL). July, 38 pp.
- Tennant D, 2007b. Potential intakes of aluminium resulting from the use of natural colours lakes. Food Chemical Risk Analysis. September, 8 pp.
- TemaNord, 2002. Food additives in Europe 2000; Status of safety assessments of food additives presently permitted in the EU. TemaNord 2002. 560, 198–201.
- Tian Q, Giusti MM, Stoner GD and Schwartz SJ, 2006. Urinary Excretion of Black Raspberry (Rubus occidentalis) Anthocyanins and Their Metabolites. Agricultural and Food Chemistry, 54, 1467–1472.
- Varma SD and Kinoshita JH, 1976. Inhibition of lens aldose reductase by flavanoids - their possible role in the prevention of diabetic cataracts. Biochemical Pharmacology 25, 2505–2513 (as referred to by JECFA, 1982).
- Wu X, Cao G and Prior RL, 2002. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. Journal of Nutrition, 132, 1865–71.
- Wu X, Pittman 3rd HE and Prior RL, 2004. Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs. Journal of Nutrition, 134, 2603–10.
- Wu X, Pittman III HE, McKay S and Prior RL, 2005. Aglycones and Sugar Moieties Alter Anthocyanin Absorption and Metabolism after Berry Consumption in Weanling Pigs. Journal of Nutrition, 135, 2417–2424.
- Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE and Prior RL, 2006a. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. Journal on Agricultural and Food Chemistry, 54, 4069–4075.
- Wu X, Pittman 3rd HE and Prior RL, 2006b. Fate of anthocyanins and antioxidant capacity in contents of the gastrointestinal tract of weanling pigs following black raspberry consumption. Journal on Agricultural and Food Chemistry, 54, 583–9.