A four-arm stone trial that shows which half of the combination is working

Design

Four-arm randomised controlled prospective trial over 12 weeks, all arms on guideline basic treatment

Population

100 patients with kidney stones at a single Shanghai hospital, July 2025 to March 2026

Primary outcome

Total effective rate of stone treatment, with urinary metabolic, oxidative stress and renal tubular markers

Effect

Effective rate 28% control, 76% herbal formula, 80% combination, 32% hydrogen-rich water alone

This trial deserves credit for its design: 100 patients with kidney stones at a Shanghai hospital were randomised four ways — to a traditional Chinese medicine formula (Ye-Shi-Shi-Lin-Formula), to hydrogen-rich water, to both, or to neither — all on top of guideline-based basic treatment, for 12 weeks. A factorial layout of that kind is the right way to find out whether a combination's effect belongs to one component, the other, or the pair.

The answer here is unusually clear, and it is not the one the title leads with. Total effective rates were 28% in the control arm, 76% with the herbal formula alone, 80% with the combination, and 32% with hydrogen-rich water alone. Hydrogen-rich water on its own performed essentially like no additional treatment; adding it to the formula moved the result by four percentage points in 25 patients per arm, which is well inside the noise. The secondary findings follow the same pattern — the formula altered oxidative stress markers, uric acid and urinary magnesium and improved tubular function markers, while hydrogen water alone shifted only glutathione reductase.

For practice the honest reading is that nothing here changes stone management, and the paper is most useful as a worked example of how a combination gets credit for its stronger component. 'Total effective rate' is also a composite that the abstract does not define, which limits what can be concluded even about the formula. In Indian practice the relevant transfer is not this formula but the same question about widely used ayurvedic stone preparations — which deserve exactly this four-arm treatment and have rarely had it.

• Keep fluid intake, dietary sodium and stone-specific metabolic management as the basis of prevention.
• Ask about herbal and proprietary stone remedies — many patients take them alongside prescribed treatment.
• Do not recommend hydrogen-rich water; it performed like the control arm.
• Treat 'total effective rate' as uninterpretable unless the composite is defined.
• Send stones for composition analysis where facilities allow — it changes prevention more than any adjunct.

Why it matters

The design answers a question most combination trials avoid: which ingredient is doing the work.

Don't overread it

A single-centre trial of 25 patients per arm with an undefined composite endpoint cannot establish the formula's efficacy either.

The statistics, in plain English

With 100 patients split four ways, each arm holds about 25 people, so a single arm's 'effective rate' carries a confidence interval spanning roughly 20 percentage points either side. That is why the 76% versus 80% comparison between the formula alone and the combination cannot support a claim that adding hydrogen water helps — the difference is one or two patients. The comparison that does survive the small numbers is the formula against control, 76% against 28%, which is a large enough gap to be unlikely to be chance even in a trial this size.

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