Hydrogen-rich water and caffeine for alertness and brain metabolism in sleep-deprived habitual coffee drinkers
Todorovic N, Zanini D, Stajer V, Korovljev D, Ostojic J, Ostojic SM. · Food Science & Nutrition. 2021;9(9):5139–5145.
Study at a glance
Human
Healthy habitual coffee drinkers aged 18–30 after 24 hours of supervised sleep deprivation and 12 hours of fasting.
A single 500 mL drink of hydrogen-rich water, prepared from a magnesium tablet and consumed in the morning. · 8 ppm dissolved H₂; the article states that drink concentration was measured by gas chromatography.
Single dose with outcomes measured 15 minutes later.
Trail-making time favored H₂ water and H₂-plus-caffeine versus control; symbol-digit errors favored H₂ water or caffeine versus control. Caffeine outperformed H₂ for reaction time. The authors reported no significant overall alertness differences among interventions, and brain oxygenation, total hemoglobin and peripheral oxygen saturation were null. Selected brain choline-to-creatine ratios changed; no participant reported an adverse effect.
Small acute study with multiple behavioral and spectroscopy outcomes, only a 15-minute follow-up and possible caffeine-withdrawal effects in habitual coffee drinkers. HRW Natural Health Products supplied the tablets and supported the work, alongside Serbian public and academic organizations; authors declared no conflicts.
What kind of evidence is this?
Human
Randomized controlled four-condition crossover trial
Other neurological conditions
H₂-rich water
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Healthy habitual coffee drinkers aged 18–30 after 24 hours of supervised sleep deprivation and 12 hours of fasting.
16 adults: 8 men and 8 women; mean age 24.0±3.5 years. All completed all four visits.
Single dose with outcomes measured 15 minutes later.
A single 500 mL drink of hydrogen-rich water, prepared from a magnesium tablet and consumed in the morning.
H₂ dissolved in water — not inhaled gas and not Brown's gas.
8 ppm dissolved H₂; the article states that drink concentration was measured by gas chromatography.
500 mL control water, 50 mg caffeine in water and H₂-rich water plus 50 mg caffeine; drinks were matched for magnesium and separated by seven-day washouts.
Outcomes and reported result
Visual and computerized alertness tests, trail-making and symbol-digit tests, brain and peripheral oxygenation, magnetic-resonance spectroscopy metabolites and self-reported adverse effects.
Trail-making time favored H₂ water and H₂-plus-caffeine versus control; symbol-digit errors favored H₂ water or caffeine versus control. Caffeine outperformed H₂ for reaction time. The authors reported no significant overall alertness differences among interventions, and brain oxygenation, total hemoglobin and peripheral oxygen saturation were null. Selected brain choline-to-creatine ratios changed; no participant reported an adverse effect.
The complete Wiley/PMC article, all four drinks, alertness table, oxygenation nulls, spectroscopy methods and regional results, adverse events, funding and conflicts were checked.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Small acute study with multiple behavioral and spectroscopy outcomes, only a 15-minute follow-up and possible caffeine-withdrawal effects in habitual coffee drinkers. HRW Natural Health Products supplied the tablets and supported the work, alongside Serbian public and academic organizations; authors declared no conflicts.
Healthy young sleep-deprived habitual coffee drinkers after one dose; not evidence for treating a neurological disorder or chronic sleep loss.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 34532023 · DOI: 10.1002/fsn3.2480
Open-access full article on PubMed Central.
Wiley open-access article on PMC plus PubMed metadata; full-text and article-status check completed 8 August 2026.
10 August 2026
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