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

Daniele Wikoff, Brian T. Welsh, Rayetta Henderson, Gregory P. Brorby, Janice Britt, Esther Myers, Jeffrey Goldberger, Harris R. Lieberman, Charles O'Brien, Jennifer Peck, Milton Tenenbein, Connie Weaver, Seneca Harvey, Jonathan Urban, Candace Doepker

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)585-648
Number of pages64
JournalFood and Chemical Toxicology
Volume109
DOIs
StatePublished - Nov 1 2017

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systematic review
pregnant women
caffeine
Caffeine
Pregnant Women
adverse effects
Population
Health
Canada
Toxicity
Bone
Research
bones
weight-of-evidence
Bone and Bones
risk behavior
Preexisting Condition Coverage
Pharmacokinetics
acute effects
Vulnerable Populations

Keywords

  • Behavior
  • Caffeine
  • Coffee
  • Pregnancy
  • Safety
  • Systematic review

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. / Wikoff, Daniele; Welsh, Brian T.; Henderson, Rayetta; Brorby, Gregory P.; Britt, Janice; Myers, Esther; Goldberger, Jeffrey; Lieberman, Harris R.; O'Brien, Charles; Peck, Jennifer; Tenenbein, Milton; Weaver, Connie; Harvey, Seneca; Urban, Jonathan; Doepker, Candace.

In: Food and Chemical Toxicology, Vol. 109, 01.11.2017, p. 585-648.

Research output: Contribution to journalArticle

Wikoff, D, Welsh, BT, Henderson, R, Brorby, GP, Britt, J, Myers, E, Goldberger, J, Lieberman, HR, O'Brien, C, Peck, J, Tenenbein, M, Weaver, C, Harvey, S, Urban, J & Doepker, C 2017, 'Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children', Food and Chemical Toxicology, vol. 109, pp. 585-648. https://doi.org/10.1016/j.fct.2017.04.002
Wikoff, Daniele ; Welsh, Brian T. ; Henderson, Rayetta ; Brorby, Gregory P. ; Britt, Janice ; Myers, Esther ; Goldberger, Jeffrey ; Lieberman, Harris R. ; O'Brien, Charles ; Peck, Jennifer ; Tenenbein, Milton ; Weaver, Connie ; Harvey, Seneca ; Urban, Jonathan ; Doepker, Candace. / Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. In: Food and Chemical Toxicology. 2017 ; Vol. 109. pp. 585-648.
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AU - Britt, Janice

AU - Myers, Esther

AU - Goldberger, Jeffrey

AU - Lieberman, Harris R.

AU - O'Brien, Charles

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AU - Harvey, Seneca

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