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

Transcription

1 Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children: Acute Health Outcome M I LTO N T E N E N B E I N, M D U N I V E R S I T Y O F M A N I T O B A 1

2 Disclosure Member of the ILSI North America Caffeine Systematic Review Team ILSI North America provided an honorarium and travel funds to attend this meeting. 2

3 PECO Questions for the Acute Health Outcome For [population], is caffeine intake above [dose], compared to intakes [dose] or less, associated with adverse acute outcomes? Population* Healthy Adults Healthy Adults Exposure > 400 mg/day > 10 g Comparator 400 mg/day 10 g Outcome Acute, nonlethal effects Death Example: For healthy adults, is caffeine intake above 400 mg/day, compared to intakes of 400 mg/day or less, associated with acute adverse outcomes? * Comparators not identified by Nawrot et al for other populations 3

4 Characterization of Data for Acute Health Outcome Data Type Characterization Number of studies Study types* Populations 26 included; 20 excluded Case reports and case series Adults, pregnant women, adolescents Exposure Mostly self-reports with poor exposure characterization Voluntary and intentional consumption Few repeated exposures ~1/2 specifically evaluated caffeine (powder or tablet); others involved energy drinks or cola Outcome (Endpoints) Death, non-fatal effects associated with suicide attempts or high-dose related events (e.g., cardiovascular events; nausea; vomiting; seizures; hypokalemia) * Study types included only for acute endpoint on basis of rare effects 4

5 Considerations re: Fatal Doses For all drugs, published doses are not precise Data are based on observation, not on the scientific method Derived from case reports of suicide gestures where the dose history is unreliable Controlled studies are not possible These considerations also apply to establishing the adverse effect dose 5

6 Death The evidence demonstrates that in adolescents and adults, deaths occurred at doses mostly > 10g/day Most exposures were suicidal gestures Adverse effects in non-fatal cases included nausea, vomiting, and cardiovascular events Exposure characterization was poor Very low to low level of confidence in the body of evidence 6

7 Non-fatal Effects Most non-fatal effects of caffeine occurred at doses > 400 mg/day Reporting bias due to nature of study types (case studies associated with effects) Most exposures were NOT suicidal gestures Adverse effects typically included nausea, vomiting, hypokalemia, seizure, and cardiovascular events (e.g. tachycardia, palpitations, changes in blood pressure) Exposure characterization was poor Very low to low level of confidence in the body of evidence 7

8 Evaluation of Individual Study Quality (Risk of Bias) Overall high risk of bias for studies in adults; few qualified studies in other populations, none in children Limited greatly by exposure characterization Q8: Unintended Q11: Other, purity +2: Definitely low +1: Probably low -1: Probably high -2: Definitely high 8

9 Factors that increased or decreased confidence in the body of evidence by endpoint Endpoint No. of Studies Initial Confidence Rating Based on study type and study features (OHAT, 2015) Overall RoB Domain-based evaluation of risk of bias per the OHAT RoB tool (OHAT, 2015) Indirectness Was the study designed to evaluate the PECO? Magnitude Strength of effect (when effect observed below the comparator) Confounding Were plausible confounders that would change the observed effect accounted for? Consistency Were findings consistent in demonstrating effects or lack of effects at or below the comparator Final Confidence Rating What is the overall rating when factors that increase or decrease confidence were considered Death 14 Very low to low Not Evaluated /- Very low to low Other acute effects 18 Very low to low Not Evaluated /- Very low to low increased confidence - no change to confidence decreased confidence 9

10 Weight of Evidence Conclusion: Acute Adults: When the weight of evidence was considered, 400 mg caffeine/day (2.5 mg/kg/day for adolescents) was not associated with acute adverse effects. Wide range of adverse effects observed across cases, with overlap Death has been associated with acute exposures of 10g or more Only a single report of death following a dose less than 10g Acute effects may be a result of rapid consumption and do not represent typical consumer behavior Pregnant Women & Children: insufficient evidence to develop a conclusion 10

11 Future Research Needs Improved exposure characterization (i.e., testing of blood concentrations) 11