Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children

Abstract

To date, one of the most heavily cited assessments of caffeine safety in the peer-reviewed literature is that issued by Health Canada (Nawrot et al., 2003). Since then, >10,000 papers have been published related to caffeine, including hundreds of reviews on specific human health effects; however, to date, none have compared the wide range of topics evaluated by Nawrot et al. (2003). Thus, as an update to this foundational publication, we conducted a systematic review of data on potential adverse effects of caffeine published from 2001 to June 2015. Subject matter experts and research team participants developed five PECO (population, exposure, comparator, and outcome) questions to address five types of outcomes (acute toxicity, cardiovascular toxicity, bone and calcium effects, behavior, and development and reproduction) in four healthy populations (adults, pregnant women, adolescents, and children) relative to caffeine intake doses determined not to be associated with adverse effects by Health Canada (comparators: 400 mg/day for adults [10 g for lethality], 300 mg/day for pregnant women, and 2.5 mg/kg/day for children and adolescents). The a priori search strategy identified >5000 articles that were screened, with 381 meeting inclusion/exclusion criteria for the five outcomes (pharmacokinetics was addressed contextually, adding 46 more studies). Data were extracted by the research team and rated for risk of bias and indirectness (internal and external validity). Selected no- and low-effect intakes were assessed relative to the population-specific comparator. Conclusions were drawn for the body of evidence for each outcome, as well as endpoints within an outcome, using a weight of evidence approach. When the total body of evidence was evaluated and when study quality, consistency, level of adversity, and magnitude of response were considered, the evidence generally supports that consumption of up to 400 mg caffeine/day in healthy adults is not associated with overt, adverse cardiovascular effects, behavioral effects, reproductive and developmental effects, acute effects, or bone status. Evidence also supports consumption of up to 300 mg caffeine/day in healthy pregnant women as an intake that is generally not associated with adverse reproductive and developmental effects. Limited data were identified for child and adolescent populations; the available evidence suggests that 2.5 mg caffeine/kg body weight/day remains an appropriate recommendation. The results of this systematic review support a shift in caffeine research to focus on characterizing effects in sensitive populations and establishing better quantitative characterization of interindividual variability (e.g., epigenetic trends), subpopulations (e.g., unhealthy populations, individuals with preexisting conditions), conditions (e.g., coexposures), and outcomes (e.g., exacerbation of risk-taking behavior) that could render individuals to be at greater risk relative to healthy adults and healthy pregnant women. This review, being one of the first to apply s...

Caffeine and energy drink use by combat arms soldiers in Afghanistan as a countermeasure for sleep loss and high operational demands

“…3,28,29 For all analyses, soldiers were divided into three categories defined as non-users and very low caffeine users (≤52 mg or the equivalent of 1 cup of tea or soda), moderate users (>52 and <400 mg or up to two energy drinks and one soda, or three cups of coffee) and heavy daily consumers (>400 mg). The use of 400 mg to separate moderate and heavy consumers of caffeine is consistent with a conservative upper limit for caffeine consumption proposed by Nawrot et al 30 and confirmed by Wikoff et al 31 for lack of adverse health effects associated with daily caffeine intake. A series of questions regarding sleep, customized for the unique nature of the combat environment, were included in the survey ( Table 1).…”

Are energy drinks suitable for children?

“…The review found limited and sometimes inconsistent data regarding the effect of caffeine intake on outcomes in children and adolescents, but the authors concluded that a caffeine dose of around 2.5 mg/kg/bodyweight/day remained an appropriate recommendation (Wikoff et al . ); another recent systematic review came to the same conclusion (Ruxton ).…”

“…A more recent systematic review (Wikoff et al . ), an update to a previous 2003 review on caffeine by Health Canada (Nawrot et al . ), considered the various effects of caffeine intake (acute toxicity, cardiovascular effects, behavioural and developmental effects) in children and adolescents, alongside other population groups.…”

Attempted suicide by caffeine tablet overdose in a 14‐year‐old girl

“…The cases of six adolescent patients aged 15–18 years with acute intoxication due to caffeine overdose have been reported in a recent review article . Three of the reported cases were related to attempted suicide via caffeine tablets . To the best of our knowledge, the present patient is the youngest to have attempted suicide by caffeine overdose obtained commercially.…”

“…Overexposure to caffeine via energy drinks or supplements is a worldwide social problem not only in adults, but also in children, including adolescents . The cases of six adolescent patients aged 15–18 years with acute intoxication due to caffeine overdose have been reported in a recent review article . Three of the reported cases were related to attempted suicide via caffeine tablets .…”