Caffeine

Authors:

Christophe Bernard, Jennifer L Temple

Findings:

This comprehensive review concludes caffeine is relatively safe for healthy adults (up to 400mg/day), but poses risks for vulnerable groups like pregnant women (recommended <200-300mg/day due to links with miscarriage/low birth weight), children/adolescents (lower safe thresholds, concerns about energy drinks), and potentially those with mental illness or heart conditions. Caffeine affects cardiovascular function (dose-dependent BP/HR changes), sleep, cognition (complex effects, withdrawal reversal noted), and can interact with alcohol and medications; withdrawal syndrome is recognized.

Participants:

Humans across the lifespan (neonates, infants, children, adolescents, adults, elderly), including healthy individuals and vulnerable populations (pregnant/lactating women, individuals with heart conditions or mental illness). Specific groups mentioned include men, women, college students, African-American and Caucasian children. Animal studies (mice, rats) also cited.

Dosage:

General safe intake for healthy adults suggested up to 400mg/day. Lower limits recommended for vulnerable groups: <200mg/day (ACOG) or <300mg/day (EC/Health Canada) for pregnant women; 100mg/day (adolescents) and 2.5mg/kg/day (children) suggested thresholds (Nawrot et al., 2003; Seifert et al., 2011). Doses >200mg/day linked to reproductive risks (miscarriage, low birth weight). Caffeine intoxication criteria mention >250mg. Specific product doses cited (e.g., soda ~45mg, coffee ~100mg/cup, energy drinks 77-80mg up to >500mg, medications 30-200mg).

Study Quality Assessment:

Comprehensive review evaluating clinical trials, observational studies, systematic reviews, meta-analyses, and expert reviews. Mentions specific methodologies (e.g., dose-response, placebo-controlled, NHANES data, serum caffeine measurement, self-report, food diaries) and limitations (e.g., reliance on self-report, recall bias, confounding variables, lack of RCTs in some areas, heterogeneity in study designs/doses, lack of data on pre-existing conditions in some reports). Cites recommendations from health authorities (e.g., FDA, IOM, AAP, EFSA, Health Canada, ACOG, IARC). Authors' funding sources disclosed (NIH, ANR).

All Effects:

Study Quality Assessment:

Systematic review and meta-analysis of prospective cohort studies. Used PubMed database.

Authors:

Institute of Medicine (US) Committee on Military Nutrition Research, Marriott BM, editor

Participants:

bachelor of medicine and bachelor of surgery

Study Quality Assessment:

Randomized controlled trial (RCT)

Findings:

Adenosine decreases neuronal firing and neurotransmitter release via A1 receptors. Via A2a receptors, adenosine, and consequently caffeine, can influence dopaminergic neurotransmission. Caffeine can also induce rapid changes in gene expression.

All Effects:

Findings:

This literature review found mixed results regarding caffeine's effects on cognitive function. Current research suggests caffeine may affect mood (potentially increasing anxiety, vigor, alertness, jitteriness; decreasing tiredness, sadness), enhances processing speed, but does not significantly affect attention. Most reviewed studies indicate positive effects on memory (short-term, long-term, working memory reaction time, information retrieval) in adults and the elderly, but potential negative effects on memory and processing speed were noted in children.

Participants:

Literature review summarizing studies involving humans (various age groups including children 9-10 yrs, young adults 18-40 yrs, adults 18-65 yrs, elderly 65-74 yrs; specific groups like medical students, e-sport players; sample sizes ranging from N=9 to N=434,900) and animals (rats).

Dosage:

Review covers studies using various caffeine sources and doses: specific single doses (65mg, 80mg, 130mg, 147.2mg, 149.5mg, 155mg, 180mg, 200mg) from coffee, energy drinks (Red Bull, 5 Hour Energy, Ai Reload), or capsules; chronic consumption levels (<1 cup to >3 cups per day); average daily intake in children (13.00 ± 43.73 mg/day). Dose-dependent effects on mood (vigor, anxiety) mentioned.

Study Quality Assessment:

Literature review summarizing multiple studies. Methodologies mentioned for summarized studies include: randomized controlled trials (RCT), double-blind, placebo-controlled, cross-over designs, cross-sectional, population-based using large biobanks (UK Biobank, ABCD study, ELSA-Brasil), specific assessment tools (POMS, STAI, VAS, CogTrack, Trail-making tests, N-Back Task, Eriksen Flanker Test, Go/No-go, Psychomotor Vigilance Test, Keep Track task), objective measures (salivary cortisol), statistical analyses (ANOVA, t-tests, regression). Acknowledges mixed results, need for larger sample sizes, and potential limitations (e.g., small sample size in one study [17]).

All Effects:

Findings:

This systematic review evaluated data from 380 studies (published 2001-2015) to determine if caffeine intake levels deemed safe by Health Canada in 2003 remain appropriate for healthy adults, pregnant women, adolescents, and children across five outcome areas (acute toxicity, cardiovascular, bone & calcium, behavior, development/reproduction). The review generally confirmed that intakes up to 400 mg/day for healthy adults, 300 mg/day for healthy pregnant women, and 2.5 mg/kg body weight/day for healthy children and adolescents are not associated with overt adverse health effects. While some effects were noted below these levels (e.g., physiological changes, effects in subgroups or under specific conditions like near bedtime), the overall weight of evidence supports these levels for healthy populations.

Participants:

Healthy adults, healthy pregnant women, healthy adolescents (aged 12–19 years), and healthy children (aged 3–<12 years).

Dosage:

Evaluated safety levels based on Health Canada (2003): up to 400 mg/day for healthy adults, 300 mg/day for healthy pregnant women, 2.5 mg/kg body weight/day for healthy children and adolescents. Acute toxicity comparator: 10 g/day.

Study Quality Assessment:

Systematic review conducted using IOM standards and guidance; protocol registered on PROSPERO (nos. CRD42015026704, CRD42015027413, CRD42015026673, CRD42015026609, CRD42015026736); searched PubMed, EMBASE, Cochrane Database (studies published June 2001-June 2015); screened >5000 articles, included 381 studies; used DistillerSR software; employed PECO framework; critically appraised individual studies using National Toxicology Program’s OHAT Risk of Bias Rating Tool; used a weight-of-evidence approach (based on IOM, NTP, GRADE) considering study quality, consistency, adversity level, magnitude of response; involved multidisciplinary scientific review team and scientific advisory board (SAB); data deposited in AHRQ SRDR. Strengths mentioned: transparency, rigor, large evidence base, multidisciplinary team. Weaknesses/Limitations acknowledged: complexity and heterogeneity of evidence, difficulty assessing chronic exposure for some endpoints, potential confounding, potential biases (pregnancy signal, recall bias), uncertainty in exposure characterization. Funding sources (ILSI North America, ABA, NCA) and potential conflicts of interest disclosed.

All Effects:

Findings:

Caffeine's behavioral effects are likely primarily due to its antagonism of A1 and A2a adenosine receptors in the central nervous system. Other potential biochemical mechanisms (calcium release, phosphodiesterase inhibition, GABA receptor blockade) are mentioned but implied to be less significant.

All Effects: