Scientific Opinion on Flavouring Group Evaluation 49, Revision 1 (FGE.49Rev1): xanthine alkaloids from the priority list

Abstract

Following a request from the European Commission, the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) was requested to deliver a scientific opinion on the safety assessment of the flavouring substances caffeine .016] and theobromine .032] in the Flavouring Group Evaluation 49, Revision 1. Consequent to the 2015 scientific opinion from the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the safety of caffeine from all dietary sources, the CEF Panel considered it inappropriate to evaluate the two substances through the Procedure. For caffeine, the Panel based its assessment on the safety threshold of 5.7 mg/kg body weight (bw) per day for adults, except pregnant/lactating women, and 3 mg/kg bw per day for children, adolescents, pregnant and lactating women, as established by the NDA Panel. The safety evaluation of theobromine takes into account that approximately 11% of an oral dose of caffeine is metabolised to theobromine and that both substances have a similar pharmacological profile. For the exposure assessment, a brand loyalty model was chosen. In this model, it was assumed that a consumer is exposed on a long-term basis to a specific category of food (i.e. non-alcoholic beverages), containing caffeine or theobromine at their respective maximum use levels. For the rest of the categories, normal use levels applied. Daily dietary exposure to caffeine and theobromine (excluding systemic exposure) added as a chemically defined flavouring substance ranged 0-2.3 and 0-0.4 mg/kg bw, respectively, across all population groups. The Panel concluded that caffeine .016] and theobromine .032] would not be expected to present safety concern based on their estimated levels of intake from their use as flavouring substances.

In Vitro Bioaccessibility and Functional Properties of Phenolic Compounds from Enriched Beverages Based on Cocoa Bean Shell

“…In fact, while in clinical studies of with a three-to four-week duration, dose levels of 150 mg theobromine/day (1.5-2.1 mg/kg bw) were well tolerated and adverse effects (such as nausea, vomiting, headache and diarrhoea) were only observed from doses higher than 500 mg theobromine/day, an actual level of no safety concern in humans has not yet been identified; however, the EFSA suggests that it is probably higher than 150 mg/day [39]. Based on these findings, the EFSA decided to derive its reference dose from the caffeine data since the results of pharmacokinetics studies of caffeine and its metabolites suggest that about 11% of caffeine oral intake is converted into theobromine and the two substances show a similar pharmacological profile [39]. Moreover, although the pharmacological effects of caffeine and theobromine can overlap, the latter shows a much lower potency than caffeine with respect to effects on the central nervous system, kidneys, or heart [39].…”

“…Based on these findings, the EFSA decided to derive its reference dose from the caffeine data since the results of pharmacokinetics studies of caffeine and its metabolites suggest that about 11% of caffeine oral intake is converted into theobromine and the two substances show a similar pharmacological profile [39]. Moreover, although the pharmacological effects of caffeine and theobromine can overlap, the latter shows a much lower potency than caffeine with respect to effects on the central nervous system, kidneys, or heart [39]. Therefore, the EFSA predicts a level of 0.6 mg/kg bw per day for healthy adults and 0.3 mg/kg bw per day for pregnant and lactating women, adolescents, and children to be of no safety concern [39] but also suggests that exceeding these doses would not necessarily result in a health risk.…”

“…Moreover, although the pharmacological effects of caffeine and theobromine can overlap, the latter shows a much lower potency than caffeine with respect to effects on the central nervous system, kidneys, or heart [39]. Therefore, the EFSA predicts a level of 0.6 mg/kg bw per day for healthy adults and 0.3 mg/kg bw per day for pregnant and lactating women, adolescents, and children to be of no safety concern [39] but also suggests that exceeding these doses would not necessarily result in a health risk. In view of this, considering that their values of caffeine and theobromine are lower than the recommended doses, both capsule and tea bag beverages could be considered safe for human health and are not expected to cause negative effects generally associated with overconsumption of these two methylxanthines, such as insomnia, anxiousness, tachycardia and nausea [37,39].…”