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The latest here:
Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children
- Under a Creative Commons license
Open Access
Highlights
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- Conducted systematic review of the potential adverse effects of caffeine consumption in healthy populations.
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- Included evaluation of cardiovascular, behavioral, reproductive & developmental, bone & calcium, and acute effects.
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- Evidence supported consumption of ≤400 mg/day in adults is not associated with overt, adverse effects.
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- Intakes of ≤300 mg/day in pregnant women and ≤2.5 mg/kg-day in children and adolescents remain acceptable.
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- Findings support shift in future research to unhealthy populations, sensitive populations and interindividual variability.
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 systematic review methodologies to
toxicological assessments, also highlights the need for refined guidance
and frameworks unique to the conduct of systematic review in this
field.
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