Following a request from the Commission, the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) has been asked to evaluate the safety-in-use of taurine and D-glucurono-gamma-lactone as constituents of the so-called “energy” drinks.
In the present opinion the Panel evaluates the safety of taurine and D-glucurono-γ-lactone as individual ingredients of so-called “energy” drinks based on the new studies provided by the petitioner.
The Panel does not evaluate the safety of “energy” drinks as such.
Taurine and D-glucurono-gamma-lactone are constituents of the so-called “energy” drinks, but they also occur at much lower levels as natural ingredients in food, and they are also normal human metabolites. Previous Scientific Committee on Food (SCF) Opinions have summarized safety studies of taurine and D-glucurono-gamma-lactone, but the safety-in-use of these two ingredients at the levels of exposure expected from their use in “energy” drinks could not be established at that time.
In the absence of new chronic and acute exposure data, the exposures used in this opinion are based on the data reported by the SCF in 2003, i.e. a daily mean chronic consumption of 0.5 cans per person and a high chronic exposure at the 95th percentile of 1.4 cans per regular consumer. The Panel notes that actual exposure data on “energy” drink consumption, especially for adolescents and young adults, may need to be collected. Based on the assumption that a can contains 250 mL and 4000 mg/L taurine and 2400 mg/L D-glucurono-gamma-lactone, the SCF calculated that these values result in a mean daily exposure to 500 mg taurine (8.3 mg taurine/kg bw/day for a 60 kg person) and 300 mg D-glucurono-gamma-lactone (5.0 mg D-glucurono-gamma-lactone/kg bw/day for a 60 kg person). The 95th percentile exposure of regular users would amount to 1400 mg taurine/day (23.3 mg/kg bw/day for a 60 kg person) and 840 mg D-glucurono-gamma-lactone /day (14 mg/kg bw/day for a 60 kg person).
If it is assumed that this amount of chronic consumption is relevant to occasional exposure of children of 25 kg body weight, then their exposure (on a body weight basis) would be about 2.5 times higher than that for adults (60-65 kg body weight). It must be emphasized that these estimates relate to chronic exposures by average and high consuming adults, and would not reflect the occasional and sporadic exposure that might occur in children. If the frequency of exposure for children would be 2.5 times lower than for adults, then the average chronic exposure for children, on a body weight basis, would be the same as for adults. If children were to consume the adult intake of 0.5 and 1.4 cans per person only once per week, then the average chronic exposure to “energy” drinks and their constituents for children, on a body weight basis, would be one third of that for adults.
These estimates for the daily exposure to taurine and D-glucurono-gamma-lactone from “energy” drinks are higher than the estimated mean daily exposure to taurine from omnivore diets which was estimated to be at most 400 mg/day, and that of D-glucurono-gamma-lactone from naturally occurring sources in the diet estimated to amount to 1-2 mg/day.
The SCF Opinion of 2003 used 3 cans/day as a reasonable high (acute) consumption, this amount being higher than the 90th percentile recorded in the Austrian survey (2.6 cans/day) and being the average reported in the Irish survey for the highest number of cans consumed in a single session. The SCF also indicated that it was aware that amounts of up to 8-12 cans/day were reported by a few extreme consumers in both surveys, which would result in an intake of 4800-7200 mg D-glucurono-γ-lactone and 8000-12000 mg taurine per day, equivalent to 80-120 mg D-glucurono-γ-lactone/kg bw/day and 133-200 mg taurine/kg bw/day for a 60 kg person.
The SCF Opinion of 2003 and the recent BfR Opinion mention a number of anecdotal and case reports of acute, adverse effects, including fatalities, in individuals consuming “energy” drinks, containing caffeine, taurine and D-glucurono-gamma-lactone. In these cases “energy” drinks had either been consumed in very high amounts (1420 mL), in combination with physical exercise, or more frequently together with alcohol. The Panel considers that it is possible that the effects reported in recent publications by Iyadurai and Chung, Nagajothi et al. and Terlizzi et al. could be due to the well known side effects of high caffeine intake, while the assumption of a causal relationship with taurine intake is lacking scientific evidence.
Upon oral exposure taurine is readily bioavailable in the systemic circulation. The Panel concludes that new ADME data support the contention that oral exposure to taurine was not increasing taurine levels in the brain, because in rat studies, brain taurine levels did not increase after dosage.
The SCF already concluded in 1999 that toxicological studies did not reveal any indication for a genotoxic, teratogenic or carcinogenic potential of taurine.
It can be concluded that the NOAEL derived from a new 13-week oral neurotoxicity study in male and female rats including functional observational battery and locomotor activity tests, confirmed the NOAEL established in the prior 13-week study, described already by the SCF in 2003, of 1000 mg taurine/kg bw/day, and provided evidence for a NOAEL of 1500 mg taurine/kg bw/day for behavioural effects. The results of this study were sufficient to address the concerns raised previously, notably the observation of increased activity and possible decrements in motor skills on the rotarod.
The NOAEL of at least 1000 mg/kg bw/day for pathological changes is respectively 120-fold higher than the estimated mean and 43-fold higher than the estimated 95th percentile exposure to taurine from “energy” drinks only, when calculated for a 60 kg person. Given that taurine is a natural body constituent, the Panel concludes that these margins of safety are sufficiently large to conclude that exposure to taurine at the levels mentioned above is not of safety concern.
The SCF already concluded that the available data indicate that D-glucurono-gamma-lactone administered orally to humans is rapidly absorbed, metabolised and excreted as glucaric acid, xylitol and L-xylulose. Animals, such as rodents, which can synthesise vitamin C endogenously do so from glucuronic acid and such animals can also convert exogenously administered D-glucurono-gamma-lactone into vitamin C. However, primates, including man, and guinea pigs do not possess this metabolic pathway. The SCF concluded that for this reason, the rodent may be an inappropriate model for man in the study of the effects of D-glucurono-gamma-lactone. The Panel concludes that data in the literature indicate that synthesis of vitamin C is only a minor pathway of D-glucurono-gamma-lactone metabolism in the rat and of limited relevance to the safety assessment of exogenous D-glucurono-gamma-lactone.
In 2003 the SCF evaluated a 13-week oral toxicity rat study with D-glucurono-gamma-lactone and concluded that the cause of the kidney lesions remained unclear.
The petitioner has now provided data from a new 13-week oral (gavage versus drinking water) toxicity study of D-glucurono-gamma-lactone in rats, with specific focus on the kidneys. This study used the same rat strain as the previous study reported in the SCF Opinion of 2003. Extensive urinalysis and histopathological examinations demonstrated no treatment-related effects. Based on the results of this study, the NOAEL for daily oral administration of D-glucurono-γ-lactone in rats was 1000 mg/kg bw/day, the highest dose tested.
Toxicological studies on the genotoxic, teratogenic or carcinogenic potential of D-glucurono-gamma-lactone were not available. However, D-glucurono-gamma-lactone is a normal human metabolite formed from glucose and there are no structural alerts for mutagenicity or carcinogenicity. At physiological pH it is in equilibrium with glucoronic acid, its immediate precursor. D-glucurono-gamma-lactone and its hydrolysis product glucuronic acid are endogenous metabolites in humans and other mammals, they occur naturally in several dietary sources and are readily metabolized to innocuous products and excreted. Furthermore, in the high dose 13-week rat studies there was no evidence of any effect on the gonads which might indicate the need for reproductive toxicity studies.
The NOAEL for D-glucurono-gamma-lactone of 1000 mg/kg bw/day is 200-fold higher than the estimated mean and 71-fold higher than the estimated 95th percentile exposure to D-glucurono-gamma-lactone from “energy” drinks only, when calculated for a 60 kg person.
Given the fact that D-glucurono-gamma-lactone is a natural body constituent the Panel concludes that these margins of safety are sufficiently large to conclude that exposure to D-glucurono-gamma-lactone at the levels mentioned above is not of safety concern.
Overall, the Panel concludes that the exposure to taurine and D-glucurono-gamma-lactone at the levels currently used in “energy” drinks and mentioned in the present opinion is not of safety concern.
The ANS Panel agrees with the considerations of the SCF Opinion from 2003 on the fact that it is unlikely that D-glucurono-γ-lactone would have any interaction with caffeine, taurine, alcohol or the effects of exercise. The Panel also concludes, based on the new data available, that additive interactions between taurine and caffeine on diuretic effects are unlikely. Other interactions between taurine and caffeine were not investigated.