Caffeine Research

Early versus Late Caffeine Therapy Administration in Preterm Neonates: An Updated Systematic Review and Meta-Analysis

Karlinski Vizentin V et al. • Neonatology (2024)

As compared with late caffeine administration, early caffeine is associated with a reduction in BPD, IVH, ROP, late-onset sepsis, and PDA in preterm neonates, albeit increased mortality.

• A total of 122,579 patients from 11 studies were included, 2 were randomized controlled trials (RCTs), and 63.9% of the neonates received early caffeine administration.
• The composite outcome of BPD or death was also lower in the early caffeine group (OR: 0.76; 95% CI: [0.66-0.88]; p < 0.0003).
• Mortality rate was higher in the early caffeine group (OR: 1.20; 95% CI: 1.12-1.29; p < 0.001).

Caffeine and IBD Risk: A Meta-Analysis

Wu X et al. • Journal of gastroenterology and hepatology (2026)

The relationship between caffeine intake and IBD risk varies by region, age, caffeine source, smoking, and education level.

• The meta-analysis showed no significant association between caffeine intake and IBD (RR = 0.84, 95% CI = 0.68-1.04).
• In Americans, caffeine increased UC risk by 68% (RR = 1.68, 95% CI = 1.17-2.42).
• Age analysis showed caffeine increased IBD risk by 4.52 times in those ≤18 (RR = 4.52, 95% CI = 1.59-12.88) but decreased risk by 7% in those >18 (RR = 0.93, 95% CI = 0.73-1.18).

Effect of Acute Caffeine Intake on the Fat Oxidation Rate during Exercise: A Systematic Review and Meta-Analysis

Collado-Mateo D et al. • Nutrients (2020)

However, the fitness level of the participant may modulate the magnitude of the effect of caffeine on fat oxidation during exercise.

• A subsequent meta-analysis was performed using the random effects model to calculate the standardized mean difference (SMD).
• The meta-analysis revealed that caffeine significantly (p = 0.008) increased the fat oxidation rate (SMD = 0.73; 95% CI = 0.19 to 1.27).
• This increment was consistent with a significant (p = 0.04) reduction of the respiratory exchange ratio (SMD = -0.33; 95% CI = -0.65 to -0.01) and a significant (p = 0.049) increase in the oxygen uptake (SMD = 0.23; 95% CI = 0.01 to 0.44).

Caffeine and endurance performance

Southward K et al. • Sports Medicine (2018)

Caffeine ingestion improves endurance performance by 2-4% on average.

• Significant improvement in endurance exercise
• Optimal timing 30-60 minutes before exercise
• 3-6mg/kg body weight most effective

Effects of caffeine on cognitive performance, mood, and alertness

McLellan TM et al. • Neuroscience & Biobehavioral Reviews (2016)

Caffeine improves cognitive function, particularly alertness, attention, and reaction time.

• Consistent improvements in alertness and attention
• Benefits most pronounced when fatigued
• Optimal dose range 100-300mg for most people

Caffeine and IBD Risk: A Meta-Analysis.

Wu X, Jiang J, Lu Q • J Gastroenterol Hepatol (2026)

The effects of caffeine intake on weight loss: a systematic review and dos-response meta-analysis of randomized controlled trials

Tabrizi R et al. • Critical reviews in food science and nutrition (2019)

Overall, the current meta-analysis demonstrated that caffeine intake might promote weight, BMI and body fat reduction.

• Thirteen RCTs with 606 participants were included in the meta-analyses.
• Overall, the current meta-analysis demonstrated that caffeine intake might promote weight, BMI and body fat reduction.
• Further research warranted to confirm findings

Effect of Caffeine and Nitrates Combination on Exercise Performance, Heart Rate and Oxygen Uptake: A Systematic Review and Meta-Analysis

Gilsanz L et al. • Nutrients (2024)

CAF+nitrates did not offer further benefits on exercise performance or physiological variables from the isolated intake of CAF and nitrates.

• The meta-analysis revealed that caffeine and nitrates supplementation (CAF+nitrates) did not enhance performance in time trials (TTs) over the CAF alone (g = -0.06; 95% CI = -0.46 to 0.35; p = 0.78) or nitrates alone (g = 0.29; 95% CI = -0.12 to 0.70; p = 0.17).
• CAF+nitrates did not affect heart rate during submaximal exercise trials over CAF alone (g = 0.04; 95% CI = -0.31 to 0.40; p = 0.80) or nitrates alone (g = -0.15; 95% CI = -0.50 to 0.20; p = 0.40).
• Likewise, CAF+nitrates did not affect oxygen uptake during submaximal exercise trials over CAF alone (g = -0.04; 95% CI = -0.45 to 0.37; p = 0.84) or nitrates alone (g = -0.29; 95% CI = -0.70 to 0.12; p = 0.16).

Effects of Caffeine Intake on Endurance Running Performance and Time to Exhaustion: A Systematic Review and Meta-Analysis

Wang Z et al. • Nutrients (2022)

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.

• 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).
• 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).

Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Payne ER et al. • Nutrition reviews (2025)

This meta-analysis provides evidence that theanine plus caffeine, and theanine alone, could be beneficial for cognitive and mood outcomes.

• This meta-analysis provides evidence that theanine plus caffeine, and theanine alone, could be beneficial for cognitive and mood outcomes.
• More research using tea beverages or tea-equivalent bioactive doses and research in free-living participants is needed.
• Further research warranted to confirm findings

A systematic review and meta-analysis of the association between young adults' sleep habits and substance use, with a focus on self-medication behaviours

Meneo D et al. • Sleep medicine reviews (2023)

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• Longitudinal results were inconclusive.
• We found a distinct pattern of associations between different substances and different sleep outcomes.
• Further investigation considering the multidimensionality of sleep would create a better understanding of the complex relationship between substance use and sleep health in young adults.Copyright © 2023 Elsevier Ltd.

Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis

Klevebrant L et al. • General hospital psychiatry (2022)

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.

• 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]).

Association between caffeine intake and erectile dysfunction: a meta-analysis of cohort studies

Karimi M et al. • Journal of health, population, and nutrition (2024)

The current evidence suggests no significant relationship between caffeine intake and ED, but limited studies limit conclusions.

• The results indicate that there was no significant relationship between coffee consumption and the risk of ED (relative risk [RR] = 0.94, 95% CI: 0.86-1.03; p = 0.999).
• The current evidence suggests no significant relationship between caffeine intake and ED, but limited studies limit conclusions.
• Future research should focus on larger sample sizes, standardized outcome assessments, and different dosages and forms of caffeine consumption.

Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis

Gama B et al. • Archives of disease in childhood. Fetal and neonatal edition (2024)

According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.

• Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively).
• According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.
• Further research warranted to confirm findings

The effect of caffeine on subsequent sleep: A systematic review and meta-analysis

Gardiner C et al. • Sleep medicine reviews (2023)

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• 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.

Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates

Kua KP et al. • British journal of clinical pharmacology (2017)

The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.

• Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81).
• The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.
• Further research warranted to confirm findings

Ergogenic Aids to Improve Physical Performance in Female Athletes: A Systematic Review with Meta-Analysis

López-Torres O et al. • Nutrients (2022)

More studies are needed in female athletes that measure the effects of different EAs on sports performance, such as beetroot juice, beta-alanine or sodium phosphate, as the studies to date are scarce and there are many types of EA that need to be further considered in this population, such as creatine and taurine.

• A random-effects model and the standardized mean differences (SMD) ± 95% confidence intervals (CI) were reported.
• Aerobic tests could be improved with the use of taurine, caffeine, and beta-alanine.
• No conclusive effects of beetroot juice, polyphenols, or creatine in improving aerobic performance were shown.

Caffeinated Drinks and Physical Performance in Sport: A Systematic Review

Jiménez SL et al. • Nutrients (2021)

Overall, the current systematic review provides evidence of the efficacy of caffeinated drinks as a valid form for caffeine supplementation in sport.

• Due to their composition, caffeinated sports drinks seem to be more beneficial to consume during long-duration exercise, when the drinks are used for both rehydration and caffeine supplementation.
• Energy drinks may be more appropriate for providing caffeine before exercise.
• Lastly, the magnitude of the ergogenic benefits obtained with caffeinated drinks seems similar in women and men athletes.

Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis

Oliphant EA et al. • Journal of perinatology : official journal of the California Perinatal Association (2024)

This meta-analysis examined the effects of Caffeine.

• Caffeine reduced apnea (RR 0.59; 95%CI 0.46,0.75; very low certainty) and bronchopulmonary dysplasia (0.77; 0.69,0.86; moderate certainty), with higher doses more effective.
• Caffeine had no effect on neurocognitive impairment in early childhood but possible benefit on motor function in middle childhood (0.72; 0.57,0.91; moderate certainty).
• The optimal dose remains unknown; further long-term studies, are needed.© 2024.

Effects of caffeine intake on pupillary parameters in humans: a systematic review and meta-analysis

Hartmann EV et al. • Behavioral and brain functions : BBF (2024)

This meta-analysis examined the effects of Caffeine.

• We summarize the numeric results as both differences in absolute pupil diameter and in terms of effect sizes.
• The evidence available in the literature does not provide consistent results but studies rated as valid by quality assessment suggest a small effect of caffeine on pupil parameters.
• More studies are needed using modern pupil assessment methods, robust study design, and caffeine dose-response methodology.© 2024.