Natural Compound

Caffeine

1,3,7-Trimethylxanthine

Evidence TierAWADA NOT PROHIBITED

tuneTypical Dose

100-400 mg per day

watchEffect Window

Onset in 15-45 minutes with a half-life of 3-6 hours (1.5-9h range depending on CYP1A2 genotype).

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Caffeine is a stimulant that blocks adenosine receptors and increases alertness. It is used to improve vigilance and to enhance endurance performance by lowering perceived exertion.

Strong evidence shows improved alertness, reaction time, and endurance performance, with reduced perceived effort and pain during exercise. Effects on strength and power are smaller but present in some trials. Minority observational research links habitual intake with lower risk of some neurodegenerative diseases, though confounding is possible. Sleep disruption and anxiety can offset benefits.

Non-selective adenosine receptor antagonist (A1/A2A) that blocks drowsiness signaling, increases catecholamine release, and enhances CNS arousal. The most well-characterized psychoactive compound in pharmacology.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Improves alertness and reaction time (A-tier)
  • Enhances endurance performance by 2-4% (A-tier)
  • Reduces perceived fatigue and improves sustained attention (A-tier)

Secondary Outcomes

  • Modest increase in fat oxidation rate (C-tier)
  • Cognitive enhancement across attention and vigilance tasks (B-tier)
  • Mildly increases metabolic rate

Safety

Contraindications and Interactions

Contraindications

  • Anxiety disorders
  • Cardiac arrhythmias
  • Pregnancy (>200mg/day)
  • Uncontrolled hypertension

Side effects

  • Insomnia
  • Anxiety/jitteriness/restlessness
  • Tachycardia or palpitations
  • GI upset (nausea, diarrhea, abdominal pain, reflux)
  • Headache
  • Increased blood pressure
  • Dependency and withdrawal symptoms
  • Intoxication at excessive doses

Interactions

  • CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) (Probable/Moderate) - can markedly increase caffeine half-life
  • Lithium (Probable/Moderate) - higher habitual caffeine may increase renal lithium excretion (lower levels), while abrupt reduction may increase serum lithium concentrations
  • Other stimulants/sympathomimetics incl. ephedrine (Probable/Moderate) - additive cardiovascular/CNS stimulation
  • Levothyroxine (Probable/Moderate) - concurrent caffeine can reduce absorption
  • Warfarin (Possible/Moderate) - response may vary. Monitor when intake changes substantially
  • Iron, calcium, zinc (Possible/Moderate) - concurrent caffeine may reduce absorption
  • Antiseizure medications (Possible/Moderate) - high caffeine intake may lower seizure threshold

Avoid if

  • Severe anxiety disorders
  • Uncontrolled cardiac arrhythmias or hypertension
  • Pregnancy when intake exceeds 200mg/day
  • Children and adolescents
  • People using lithium or CYP1A2-interacting medications without clinician guidance

Evidence

Study-level References

caffeine-SRC-001Umbrella Review of Meta-Analyses
Sourceopen_in_new

Grgic J, et al. "Wake up and smell the coffee: caffeine supplementation and exercise performance-an umbrella review of 21 published meta-analyses." Br J Sports Med. 2020.

Population: Athletes / Active Adults

Dose protocol: 3-6 mg/kg, 30-60 min pre-exercise

Key findings: Caffeine is a highly effective ergogenic aid across aerobic endurance, muscular strength, muscular endurance, power, jumping performance, and exercise speed. Strongest effects observed in aerobic endurance tasks.

Paper content

Caffeine is a highly effective ergogenic aid across aerobic endurance, muscular strength, muscular endurance, power, jumping performance, and exercise speed. Strongest effects observed in aerobic endurance tasks.

caffeine-SRC-002Position Stand / Systematic Review
Sourceopen_in_new

Goldstein ER, et al. "International Society of Sports Nutrition position stand: caffeine and performance." J Int Soc Sports Nutr. 2010;7(1):5.

Population: Athletes / General adults

Dose protocol: 3-6 mg/kg body weight

Key findings: Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate doses (~3-6 mg/kg). Does not further improve performance when consumed at higher doses (≥9 mg/kg). Effective for sustained maximal endurance exercise and time-trial performance.

Paper content

Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate doses (~3-6 mg/kg). Does not further improve performance when consumed at higher doses (≥9 mg/kg). Effective for sustained maximal endurance exercise and time-trial performance.

caffeine-SRC-003Review / Meta-analysis
Sourceopen_in_new

Nehlig A. "Is caffeine a cognitive enhancer?" J Alzheimers Dis. 2010;20 Suppl 1:S85-94.

Population: General adults

Dose protocol: 50-400 mg acute doses

Key findings: Caffeine improves attention, vigilance, and reaction time at doses as low as 50mg. Effects on higher-order cognitive functions (memory, executive function) are less consistent and more dose-dependent. Habitual consumers may require caffeine to restore baseline rather than enhance above it.

Paper content

Caffeine improves attention, vigilance, and reaction time at doses as low as 50mg. Effects on higher-order cognitive functions (memory, executive function) are less consistent and more dose-dependent. Habitual consumers may require caffeine to restore baseline rather than enhance above it.

Guides

Setup

Help