Risk Assessment of "Other Substances" – Caffeine

ABSTRACT

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet, NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances", VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present risk assessment of caffeine is based on previous risk assessments and articles retrieved from a literature search. According to information from NFSA, caffeine is an ingredient in food supplements and energy drinks sold in Norway. NFSA has requested a risk assessment of 100 and 300 mg/day of caffeine in food supplements, and of 32 mg/100 ml of caffeine in energy drinks. Drinking patterns reflecting a high acute intake, a mean chronic intake and a high chronic intake were assessed. The total exposure to caffeine from other sources than energy drinks, such as foods and cosmetic products, is not included in the risk assessment. The main sources of caffeine in the diet include coffee, tea, caffeinated soft drinks (including energy drinks) and chocolate. The means and 95th percentiles of daily caffeine intake from all sources for adults (from 16 EU Member States) calculated by the European Food Safety Authority (EFSA) ranged from 37 to 319 mg and from 109 to 742 mg, respectively. The median daily caffeine intake from different sources among pregnant Norwegian women, selfreported at gestational weeks 17 and 30, was 126 mg/day pre-pregnancy, 44 mg/day at gestational week 17, and 62 mg/day at gestational week 30. Caffeine is rapidly and completely absorbed after oral intake, and the peak plasma concentration can be reached within 30-120 minutes. Caffeine crosses the blood–brain barrier, the placental barrier and the blood–testicular barrier, and is excreted in breast milk. Several studies and assessments addressing safety or risk of caffeine have been performed. With regard to caffeine intake and adverse birth weight-related outcomes, these outcomes were observed at all levels of caffeine intake, with no threshold below which this relationship was not observed (EFSA, 2015). In the risk characterization, VKM has applied the intake levels considered unlikely to cause adverse health effects in the new and comprehensive risk assessment by EFSA (EFSA, 2015), also taking into account previous risk assessments and newer literature. The intake levels of caffeine for different population groups (children, adolescents, pregnant women and fetus, lactating women and the breastfed infant and adults) unlikely to cause adverse effects have been identified. For the general adult population (not including pregnant women), these levels are • Single intake of caffeine up to 200 mg (about 3 mg/kg bw for a 70-kg adult) do not give rise to safety concerns. • Intakes up to 400 mg per day (about 5.7 mg/kg bw per day for a 70-kg adult) consumed throughout the day, do not give rise to safety concerns for adults in the general population, except for pregnant women (see below). • Caffeine intake of about 1.4 mg/kg bw may increase sleep latency and reduce sleep duration in adults. For children and adolescents, these levels are • A daily intake of 3 mg/kg bw per day do not give rise to safety concerns. • Caffeine doses of about 1.4 mg/kg bw may increase sleep latency and reduce sleep duration in some children and adolescents. For pregnant women and the fetus, these levels are • 200 mg per day (about 3 mg/kg bw for a 70-kg adult) consumed throughout the day do not give rise to safety concerns. • With regard to caffeine intake and adverse birth weight-related outcomes, it was concluded that these outcomes were observed at all levels of caffeine intake, with no threshold below which this relationship was not observed. It was considered that the risk becomes clinically relevant at total daily doses of about 200 mg of caffeine from all sources. Sengpiel et al. (2013) reported that caffeine intake from different sources was associated with lower birth weight, and that caffeine intake of 200 to 300 mg/day increased the odds for the baby being small for gestational age compared to 0 to 50 mg/day. For lactating women and the breastfed infant, these levels are • Single doses of caffeine up to 200 mg (about 3 mg/kg bw) and habitual caffeine consumption at doses of 200 mg per day do not give rise to safety concerns. Food supplements From a daily dose of 100 mg caffeine, the calculated intake levels are 2.3, 1.6 and 1.4 mg/kg bw per day for children (10 to <14 years), adolescents (14 to <18 years) and adults (≥18 years), respectively. From a daily dose of 300 mg caffeine, the calculated intake levels are 6.9, 4.9 and 4.3 mg/kg bw per day for the same age groups, respectively. VKM concludes that it is unlikely that a dose of 100 mg of caffeine per day from food supplements causes adverse health effects in children (10 years and above), adolescents (14 to <18 years), pregnant women and the fetus, lactating women and the breastfed infant and adults (≥18 years). However, for children and adolescents, a dose of 100 mg per day is above the intake that may increase sleep latency and reduce sleep duration. For adults, a dose of 100 mg per day is equal to the intake that may increase sleep latency and reduce sleep duration. VKM concludes that a dose of 300 mg of caffeine per day from food supplements may represent a risk of adverse health effects in children (10 years and above), adolescents (14 to <18 years), pregnant women and the fetus and lactating women and the breastfed infant. Consumed as a single dose, 300 mg of caffeine from food supplement may represent a risk of adverse health effects in adults (≥18 years). Consumed throughout the day, it is unlikely that a dose of 300 mg of caffeine per day from food supplements causes adverse health effects in adults. A dose of 300 mg per day is above the intake that may increase sleep latency and reduce sleep duration. Energy drinks The estimated exposure to caffeine from a drinking pattern reflecting a high acute intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) is 13.9 mg/kg bw per day for children (3 to <10 years), 11.1 mg/kg bw per day for children (10 to <14 years), 10.4 mg/kg bw per day for adolescents (14 to <18 years) and 9.1 mg/kg bw per day for adults (≥18 years). VKM concludes that a drinking pattern reflecting a high acute intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) may represent a risk of adverse health effects in children (3 years and above), adolescents (14 to <18 years), pregnant women and the fetus, lactating women and the breastfed infant and adults (≥18 years). In addition, the intake is above the intake that may increase sleep latency and reduce sleep duration. The estimated exposure to caffeine from a drinking pattern reflecting a mean chronic intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) is 0.8 mg/kg bw per day for children (3 to <10 years), 0.5 mg/kg bw per day for children (10 to <14 years), 0.3 mg/kg bw per day for adolescents (14 to <18 years) and 0.3 mg/kg bw per day for adults (≥18 years). VKM concludes that it is unlikely that a drinking pattern reflecting a mean chronic intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) causes adverse health effects in children (3 years and above), adolescents (14 to <18 years), pregnant women and the fetus, lactating women and the breastfed infant and adults (≥18 years). In addition, the intake is below the intake that may increase sleep latency and reduce sleep duration. The estimated exposure to caffeine from a drinking pattern reflecting a high chronic intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) is 2.3 mg/kg bw per day for children (3 to <10 years), 1.3 mg/kg bw per day for children (10 to <14 years), 1.1 mg/kg bw per day for adolescents (14 to <18 years) and 1.5 mg/kg bw per day for adults (≥18 years). VKM concludes that it is unlikely that a drinking pattern reflecting a high chronic intake of caffeine from energy drinks (containing 32 mg caffeine/100 ml) causes adverse health effects in children (3 years and above), adolescents (14 to <18 years), pregnant women and the fetus, lactating women and the breastfed infant and adults (≥18 years). For children (3 to <10 years) and adults (≥18 years), the intake is above the intake that may increase sleep latency and reduce sleep duration. For children (10 to <14 years) and adolescents (14 to <18 years), the intake is below the intake that may increase sleep latency and reduce sleep duration.