What clinical trials have tested alkaline water for gastroesophageal reflux disease (GERD) and what were their results?
Executive summary
Three types of clinical evidence have tested alkaline or bicarbonate-rich waters for reflux: a lab-driven hypothesis and small observational cohorts led by Koufman that include in vitro pepsin work (not randomized clinical proof) [1], a 2017 cohort study combining alkaline water with a Mediterranean diet that reported symptom control comparable to proton pump inhibitors for laryngopharyngeal reflux (LPR) [2] [3], and higher‑quality randomized trials of bicarbonate‑rich mineral waters—most notably the phase‑III STOMACH STILL trial—which found that bicarbonate‑rich water reduced heartburn symptoms compared with control mineral water over weeks [4] [5]. Systematic review authors nonetheless conclude the evidence is promising but insufficient to make firm clinical recommendations [6].
1. The laboratory seed: pepsin inactivation and buffering capacity
The case for alkaline water began with biochemical experiments showing that an alkaline drinking water at roughly pH 8.8 irreversibly inactivated human pepsin in vitro and had a markedly greater hydrochloric‑acid buffering capacity than ordinary bottled waters, findings reported and discussed by Koufman and colleagues in 2012 [7] [1] [8]. Those laboratory data underpin the mechanistic claim—that raising luminal pH or delivering bicarbonate can neutralize acid and reduce the proteolytic threat of pepsin to laryngeal and esophageal tissues—but the experiments were bench studies and do not prove clinical benefit on their own [1].
2. Randomized clinical evidence: STOMACH STILL and bicarbonate‑rich mineral water trials
The most rigorous clinical data come from randomized trials of hydrogen‑carbonate (bicarbonate)‑rich mineral waters rather than branded “alkaline” bottled water per se. The phase‑III STOMACH STILL randomized, placebo‑controlled trial reported that daily consumption of bicarbonate‑rich mineral water reduced heartburn intensity, improved quality of life, and decreased need for rescue medications compared with regular mineral water over the study period [4] [5]. Systematic reviewers summarize these bicarbonate‑water trials as showing symptom reductions in intervention groups, but also note methodological limitations across several trials (small size, short follow‑up, variable control groups) [6].
3. Cohort/dietary study: alkaline water plus Mediterranean diet versus PPIs
A 2017 cohort study compared a package intervention—alkaline water plus a plant‑forward Mediterranean diet and standard reflux precautions—against standard proton pump inhibitor (PPI) therapy for laryngopharyngeal reflux and reported symptom control with the dietary/alkaline water approach that was comparable to PPI therapy [2] [3]. Authors and subsequent summaries stressed this was not a randomized trial, outcomes were largely symptom‑based, and the dietary changes likely contributed substantially to the observed benefit; the paper itself calls for randomized trials to disaggregate the effects of diet and alkaline water [2].
4. Systematic review synthesis and methodological caveats
A 2024 systematic review of clinical intervention studies on mineral/alkaline waters found that hydrogen‑carbonate mineral waters can produce a buffer reaction and some clinical trials suggested reductions in heartburn episodes, yet the reviewers judged the overall trial quality poor and concluded there is insufficient evidence to recommend mineral or alkaline water as an established therapy for heartburn or GERD [6]. The review also highlights small Russian and Ukrainian trials and spa‑based studies of variable rigor, further underscoring heterogeneity in interventions, dosages, and endpoints [6].
5. Where the evidence stands and what’s next
Taken together, mechanistic lab work (pepsin inactivation) plus randomized bicarbonate‑water trials and a cohort diet/alkaline trial point toward a plausible, modest symptomatic benefit from bicarbonate‑rich or alkaline liquids as adjuncts in reflux care, but high‑quality, placebo‑controlled randomized trials isolating alkaline water alone and measuring objective reflux markers (pH/pepsin) are still needed before changing standard practice [7] [4] [2] [6]. Readers should also note potential commercial and advocacy agendas: proponents cite bench and cohort data enthusiastically [9] [10], while systematic reviewers and gastroenterology trialists emphasize the limited and heterogenous clinical evidence [6] [4].