Posted by The question raised at the webinar held on Dec. 6, on the food application of CDs, if CD derivatives can be used in food products. See the answer below:
Fact: All parent cyclodextrins are accepted as food additives and “generally recognized as safe” (GRAS).
As dietary supplement, the total daily oral dose of α-CD may reach 6000 mg/day, for β-CD 500 mg/day and for γ-CD 10 000 mg/day, and for HP-β-CD as oral pharmaceutical 8000 mg/day (Ref: Loftsson, T., Brewster, M.E., ‘Pharmaceutical applications of cyclodextrins: basic science and product development’, J. Pharmacy and Pharmacology, Vol. 62, 2010, p. 1607-1621). In a recent evaluation of European Medicinal Agency (EMA) only the parent CDs are mentioned as food additives, the derivatives not: “In 2000-2004, α-CD, β-CD and γ-CD were introduced into the generally regarded as safe (GRAS) list of the FDA for use as a food additive. Alpha- and beta-CD are approved as novel food ingredients by the Commission. Beta-CD is approved in Europe as a food additive (E 459) with an ADI (acceptable daily intake) of 5 mg/kg/day.”
Preclinically, oral NOELs after a year of HP-β-CD are 500 mg/kg/day for rats and 1000 mg/kg/day for dogs . Ref: Gould, S., Scott, R.C., 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): a toxicology review, Food Chem Toxicol., Vol. 43(10), 2005, p. 1451-1459).
Oral NOAELs (no –observed-effect-level) of SBE-β-CD in rats and dogs after 3 months are both 3600 mg/kg/day (Ref: Stella, V.J., He, Q., Cyclodextrins, Toxicol Pathol Vol. 36, 2008, p. 30-42).
Random Methyl-β-CD has no oral application. (I have no offical data)
Not highly relevant, but may be of interest: oral safety data on children with HPBCD
Very few data on children under two years of age treated with oral solutions of itraconazol with up to 200 mg HP-β-CD/kg/day for 2 weeks were well tolerated and considered safe. The oral availability of HP-β-CD was less than 1% (Ref: Grigull, L., Kuehlke, O., Beilken, A., Sander, A., Linderkamp, C., Schmid, H., Seidemann, K., Sykora, K.W., Schuster, F.R., Welte, K., ‘Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric stem cell transplantation recipients: A pilot study for evaluation of safety and efficacy’, Pediatric Transplantation, Vol. 11(3), p. 261-266;
Ref: De Repentigny, L., Ratelle, J., Leclerc, J-M., Cornu, G., Sokal, E.M., Jacqmin, P., De Beule, K., ‘Repeated-Dose Pharmacokinetics of an Oral Solution of Itraconazole in Infants and Children’, Antimicrobial Agents and Chemotherapy, Vol. 42(2), 1998, p. 404–408).
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