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Sleep Medicine Reviews Jun 2023The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of subsequent sleep. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of subsequent sleep. This systematic review and meta-analysis investigated the effect of caffeine on the characteristics of night-time sleep, with the intent to identify the time after which caffeine should not be consumed prior to bedtime. A systematic search of the literature was undertaken with 24 studies included in the analysis. Caffeine consumption reduced total sleep time by 45 min and sleep efficiency by 7%, with an increase in sleep onset latency of 9 min and wake after sleep onset of 12 min. Duration (+6.1 min) and proportion (+1.7%) of light sleep (N1) increased with caffeine intake and the duration (-11.4 min) and proportion (-1.4%) of deep sleep (N3 and N4) decreased with caffeine intake. To avoid reductions in total sleep time, coffee (107 mg per 250 mL) should be consumed at least 8.8 h prior to bedtime and a standard serve of pre-workout supplement (217.5 mg) should be consumed at least 13.2 h prior to bedtime. The results of the present study provide evidence-based guidance for the appropriate consumption of caffeine to mitigate the deleterious effects on sleep.
Topics: Humans; Caffeine; Sleep; Polysomnography; Coffee; Sleep Deprivation
PubMed: 36870101
DOI: 10.1016/j.smrv.2023.101764 -
Nutrients Dec 2022Caffeine (1,3,7-trimethylxanthine) is one of the most widely consumed performance-enhancing substances in sport due to its well-established ergogenic effects. The use of... (Meta-Analysis)
Meta-Analysis Review
Caffeine (1,3,7-trimethylxanthine) is one of the most widely consumed performance-enhancing substances in sport due to its well-established ergogenic effects. The use of caffeine is more common in aerobic-based sports due to the ample evidence endorsing the benefits of caffeine supplementation on endurance exercise. However, most of this evidence was established with cycling trials in the laboratory, while the effects of the acute intake of caffeine on endurance running performance have not been properly reviewed and meta-analyzed. The purpose of this study was to perform a systematic review and meta-analysis of the existing literature on the effects of caffeine intake on endurance running performance. A systematic review of published studies was performed in four different scientific databases (Medline, Scopus, Web of Science, and SportDiscus) up until 5 October 2022 (with no year restriction applied to the search strategy). The selected studies were crossover experimental trials in which the ingestion of caffeine was compared to a placebo situation in a single- or double-blind randomized manner. The effect of caffeine on endurance running was measured by time to exhaustion or time trials. We assessed the methodological quality of each study using Cochrane’s risk-of-bias (RoB 2) tool. A subsequent meta-analysis was performed using the random effects model to calculate the standardized mean difference (SMD) estimated by Hedges’ g and 95% confidence intervals (CI). Results: A total of 21 randomized controlled trials were included in the analysis, with caffeine doses ranging between 3 and 9 mg/kg. A total of 21 studies were included in the systematic review, with a total sample of 254 participants (220 men, 19 women and 15 participants with no information about gender; 167 were categorized as recreational and 87 were categorized as trained runners.). The overall methodological quality of studies was rated as unclear-to-low risk of bias. The meta-analysis revealed that the time to exhaustion in running tests was improved with caffeine (g = 0.392; 95% CI = 0.214 to 0.571; p < 0.001, magnitude = medium). Subgroup analysis revealed that caffeine was ergogenic for time to exhaustion trials in both recreational runners (g = 0.469; 95% CI = 0.185 to 0.754; p = 0.001, magnitude = medium) and trained runners (g = 0.344; 95% CI = 0.122 to 0.566; p = 0.002, magnitude = medium). The meta-analysis also showed that the time to complete endurance running time trials was reduced with caffeine in comparison to placebo (g = −0.101; 95% CI = −0.190 to −0.012, p = 0.026, magnitude = small). In summary, caffeine intake showed a meaningful ergogenic effect in increasing the time to exhaustion in running trials and improving performance in running time trials. Hence, caffeine may have utility as an ergogenic aid for endurance running events. More evidence is needed to establish the ergogenic effect of caffeine on endurance running in women or the best dose to maximize the ergogenic benefits of caffeine supplementation.
Topics: Male; Humans; Female; Caffeine; Physical Endurance; Performance-Enhancing Substances; Running; Bicycling; Athletic Performance; Randomized Controlled Trials as Topic
PubMed: 36615805
DOI: 10.3390/nu15010148 -
Asia Pacific Journal of Clinical... 2018To evaluate the associations of dietary factors and the risk of gout and hyperuricemia. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
To evaluate the associations of dietary factors and the risk of gout and hyperuricemia.
METHODS AND STUDY DESIGN
PubMed and Embase databases were searched from inception to June 2017 for eligible studies. Nineteen prospective cohort or cross-sectional studies with adequate sample sizes are included, all involving red meat, seafoods, alcohol, fructose, dairy products, soy foods, high-purine vegetables and coffee.
RESULTS
Meta-analysis revealed several dietary associations with gout risk: red meat: OR 1.29 (95% CI 1.16-1.44); seafoods: OR 1.31 (95% CI 1.01-1.68); alcohol: OR 2.58 (95% CI 1.81-3.66); fructose: OR 2.14 (95% CI 1.65- 2.78); dairy products: OR 0.56 (95% CI 0.44-0.70); soy foods: OR 0.85 (95% CI 0.76-0.96); high-purine vegetables: OR 0.86 (95% CI 0.75-0.98); coffee: OR 0.47 (95% CI 0.37-0.59).Dietary association with hyperuricemia risk (red meat: OR 1.24 (95% CI 1.04-1.48); seafoods: OR 1.47 (95% CI 1.16-1.86); alcohol: OR 2.06 (95% CI 1.60-2.67); fructose: OR 1.85 (95% CI 1.66-2.07); dairy products: OR 0.50 (95% CI 0.37-0.66); soy foods: OR 0.70 (95% CI 0.56-0.88); high-purine vegetables ingestion: OR 1.10 (95% CI 0.88-1.39), P=0.39; coffee:OR0.76 in men (95% CI 0.55-1.06), OR 1.58 in women (95% CI 1.16-2.16).
CONCLUSION
The risk of hyperuricemia and gout is positively correlated with the intake of red meat, seafoods, alcohol or fructose, and negatively with dairy products or soy foods. High-purine vegetables showed no association with hyperuricemia, but negative association with gout. Coffee intake is negatively associated with gout risk, whereas it may be associated with increased hyperuricemia risk in women but decreased risk in men.
Topics: Aged; Alcoholic Beverages; Coffee; Cohort Studies; Cross-Sectional Studies; Dairy Products; Diet; Female; Gout; Humans; Hyperuricemia; Male; Middle Aged; Prospective Studies; Purines; Red Meat; Risk Factors; Seafood; Sex Factors; Soy Foods; Vegetables
PubMed: 30485934
DOI: 10.6133/apjcn.201811_27(6).0022 -
General Hospital Psychiatry 2022Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the magnitude of the effect of caffeine on anxiety and panic attacks are lacking and potential dose-response relationships have not been examined.
OBJECTIVES
In the present systematic review and meta-analysis, we aimed to examine the acute effects of placebo-controlled caffeine challenge on occurrence of panic attacks and subjective anxiety in patients with PD and healthy controls (HC), including dose-response relationships.
METHODS
Systematic searches were performed in six databases. We included blinded placebo-controlled studies of acute caffeine challenge on panic attacks and/or subjective anxiety in adult patients with PD.
RESULTS
Of the 1893 identified articles, ten met our inclusion criteria. The 9 studies investigating panic attacks included 237 patients, of which 51.1% had a panic attack following caffeine, but none after placebo. Six of these studies compared 128 patients with 115 healthy controls (HC), finding that patients (53.9%) were more vulnerable than HC (1.7%) for panic attacks following caffeine (log RR: 3.47; 95% CI 2.06-4.87). Six studies investigated subjective anxiety in 121 patients and 111 HC following caffeine, with an overall effect indicating increased sensitivity to the anxiogenic effects of caffeine in the patient group (Hedges' g = 1.02 [95% CI: 0.09-1.96]). The restricted range of caffeine employed [400-750 mg] and few studies (3) not using 480 mg prevented any meaningful analysis of a dose-response relationship.
LIMITATIONS
Of the ten studies included, only 2 reported anxiety data for the placebo condition, precluding a proper meta-analysis comparing anxiogenic effects of caffeine and placebo. The restricted dose range used prevented assessment of dose-response relationships.
CONCLUSIONS
The results confirm that caffeine at doses roughly equivalent to 5 cups of coffee induces panic attacks in a large proportion of PD patients and highly discriminates this population from healthy adults. Caffeine also increases anxiety in PD patients as well as among healthy adults at these doses although the exact relationship between caffeine-induced anxiety and panic attacks remains uncertain. The results suggest that caffeine targets important mechanisms related to the pathophysiology of PD.
IMPLICATIONS
Future studies should employ a wider range of caffeine doses and investigate contributions of biological and psychological mechanisms underlying the anxiogenic and panicogenic effects of caffeine. In the clinic, patients with PD should be informed about the panicogenic and anxiogenic effects of caffeine, with the caveat that little is known regarding smaller doses than 480 mg. Registration. PROSPERO (www.crd.york.ac.uk/prospero) registration number CRD42019120220.
Topics: Adult; Anxiety; Anxiety Disorders; Caffeine; Humans; Panic Disorder
PubMed: 34871964
DOI: 10.1016/j.genhosppsych.2021.11.005 -
Sports Health 2021Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use. (Meta-Analysis)
Meta-Analysis
CONTEXT
Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use.
OBJECTIVE
To evaluate the reported adverse effects of energy drink consumption.
DATA SOURCES
The electronic databases MEDLINE, EMBASE, and PubMed were searched for relevant studies from inception to November 2019, and pertinent data were abstracted.
STUDY SELECTION
Only clinical studies reporting adverse events after energy drink consumption were included.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 4.
DATA EXTRACTION
Data regarding sample size characteristics, energy drink characteristics, comparators, and all adverse events were extracted in duplicate and recorded.
RESULTS
A total of 32 studies and 96,549 individuals were included. Frequently reported adverse events in the pediatric population were insomnia (35.4%), stress (35.4%), and depressive mood (23.1%). Frequently reported adverse events in the adult population were insomnia (24.7%), jitteriness/restlessness/shaking hands (29.8%), and gastrointestinal upset (21.6%). Alcohol mixed with energy drinks significantly reduced the likelihood of sedation effects but increased the likelihood of stimulatory effects. Energy drink consumption significantly increased the odds of insomnia (OR, 5.02; 95% CI, 1.72-14.63) and jitteriness/activeness (OR, 3.52; 95% CI, 1.28-9.67) compared with the control group.
CONCLUSION
The authors recommend that individuals avoid frequent energy drink consumption (5-7 energy drinks/week) and avoid co-consumption with alcohol; increased regulatory standards should be placed in the sale of energy drinks, particularly with regard to the pediatric population.
Topics: Alcohol Drinking; Caffeine; Depression; Energy Drinks; Gastrointestinal Diseases; Humans; Sleep Initiation and Maintenance Disorders; Stress, Psychological
PubMed: 33211984
DOI: 10.1177/1941738120949181 -
Journal of the International Society of... 2018Caffeine is commonly used as an ergogenic aid. Literature about the effects of caffeine ingestion on muscle strength and power is equivocal. The aim of this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Caffeine is commonly used as an ergogenic aid. Literature about the effects of caffeine ingestion on muscle strength and power is equivocal. The aim of this systematic review and meta-analysis was to summarize results from individual studies on the effects of caffeine intake on muscle strength and power.
METHODS
A search through eight databases was performed to find studies on the effects of caffeine on: (i) maximal muscle strength measured using 1 repetition maximum tests; and (ii) muscle power assessed by tests of vertical jump. Meta-analyses of standardized mean differences (SMD) between placebo and caffeine trials from individual studies were conducted using the random effects model.
RESULTS
Ten studies on the strength outcome and ten studies on the power outcome met the inclusion criteria for the meta-analyses. Caffeine ingestion improved both strength (SMD = 0.20; 95% confidence interval [CI]: 0.03, 0.36; = 0.023) and power (SMD = 0.17; 95% CI: 0.00, 0.34; = 0.047). A subgroup analysis indicated that caffeine significantly improves upper (SMD = 0.21; 95% CI: 0.02, 0.39; = 0.026) but not lower body strength (SMD = 0.15; 95% CI: -0.05, 0.34; = 0.147).
CONCLUSION
The meta-analyses showed significant ergogenic effects of caffeine ingestion on maximal muscle strength of upper body and muscle power. Future studies should more rigorously control the effectiveness of blinding. Due to the paucity of evidence, additional findings are needed in the female population and using different forms of caffeine, such as gum and gel.
Topics: Athletes; Caffeine; Humans; Muscle Strength; Muscle, Skeletal; Performance-Enhancing Substances; Sports Nutritional Physiological Phenomena
PubMed: 29527137
DOI: 10.1186/s12970-018-0216-0 -
Ultrasound in Obstetrics & Gynecology :... Apr 2023Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection.
METHODS
MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy.
RESULTS
Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low.
CONCLUSIONS
Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Cytomegalovirus Infections; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Prenatal Care; Valacyclovir
PubMed: 36484439
DOI: 10.1002/uog.26136 -
Clinical Microbiology and Infection :... Sep 2022The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.
OBJECTIVES
To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements.
DATA SOURCES
Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022.
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials; all languages.
PARTICIPANTS
All hospitalized adults with COVID-19.
INTERVENTIONS
Remdesivir, in comparison to either placebo, or standard of care.
ASSESSMENT OF RISK OF BIAS
We used the ROB-2 criteria.
METHODS OF DATA SYNTHESIS
The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important.
RESULTS
We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5-1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79-0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88-1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen.
CONCLUSIONS
Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.
Topics: Adenosine Monophosphate; Adult; Alanine; Bayes Theorem; Humans; Oxygen; SARS-CoV-2; United States; COVID-19 Drug Treatment
PubMed: 35598856
DOI: 10.1016/j.cmi.2022.04.018 -
Nutrients Jun 2022Nutritional ergogenic aids (NEAs) are substances included within the group of sports supplements. Although they are widely consumed by athletes, evidence-based analysis... (Meta-Analysis)
Meta-Analysis Review
Nutritional ergogenic aids (NEAs) are substances included within the group of sports supplements. Although they are widely consumed by athletes, evidence-based analysis is required to support training outcomes or competitive performance in specific disciplines. Combat sports have a predominant use of anaerobic metabolism as a source of energy, reaching peak exertion or sustained effort for very short periods of time. In this context, the use of certain NEAs could help athletes to improve their performance in those specific combat skills (i.e., the number of attacks, throws and hits; jump height; and grip strength, among others) as well as in general physical aspects (time to exhaustion [TTE], power, fatigue perception, heart rate, use of anaerobic metabolism, etc.). Medline/PubMed, Scopus and EBSCO were searched from their inception to May 2022 for randomised controlled trials (RCTs). Out of 677 articles found, 55 met the predefined inclusion criteria. Among all the studied NEAs, caffeine (5-10 mg/kg) showed strong evidence for its use in combat sports to enhance the use of glycolytic pathways for energy production during high-intensity actions due to a greater production of and tolerance to blood lactate levels. In this regard, abilities including the number of attacks, reaction time, handgrip strength, power and TTE, among others, were improved. Buffering supplements such as sodium bicarbonate, sodium citrate and beta-alanine may have a promising role in high and intermittent exertion during combat, but more studies are needed in grappling combat sports to confirm their efficacy during sustained isometric exertion. Other NEAs, including creatine, beetroot juice or glycerol, need further investigation to strengthen the evidence for performance enhancement in combat sports. Caffeine is the only NEA that has shown strong evidence for performance enhancement in combat sports.
Topics: Athletes; Athletic Performance; Caffeine; Dietary Supplements; Humans; Performance-Enhancing Substances; Sports Nutritional Physiological Phenomena
PubMed: 35807770
DOI: 10.3390/nu14132588 -
Food and Chemical Toxicology : An... Nov 2017To 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,... (Review)
Review
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.
Topics: Adolescent; Adolescent Health; Adult; Caffeine; Child; Child Health; Female; Humans; Male; Pregnancy; Pregnancy Complications; Young Adult
PubMed: 28438661
DOI: 10.1016/j.fct.2017.04.002