Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: K⁺-enriched table salt lowers blood pressure (BP) and reduces cardiovascular mortality. Whether these beneficial effects are caused by a reduction in Na⁺ intake, increased K⁺ intake, or a combination of both is unknown. We tested the hypothesis that isolated oral KCl supplementation without parallel NaCl reduction lowers body Na⁺ and BP in patients with arterial hypertension.
Study Design and Methods: Prospective, open-label observational longitudinal trial with standardized K⁺ supplementation intervention in patients referred for routine diagnostic workup of hyperaldosteronism (HA) to Changi General Hospital, Singapore (Fig. 1). Randomization to placebo was not possible due to hypokalemia with blood [K⁺]<3.0 mmol/L in 10% of our study participants. Measurements: Na⁺, K⁺, aldosterone levels in blood and 24-h urine, muscle Na⁺ content with 23Na magnetic resonance imaging, and BP levels in 40 study participants at baseline and 6-9 weeks after blood K⁺-adjusted oral KCl supplementation (Span-K tablets; 600 mg; Fig. 2). The study was halted and reported at 50% recruitment goal because the primary and secondary endpoints were realized, and BP lowered.
Main Results: (i) Intervention confirmation and safety: Plasma K⁺-adjusted oral KCl intervention uniformly increased blood K⁺ concentration and 24-h urine K⁺ excretion without parallel changes in urine Na⁺ (Tab. 1). No study participant developed hyperkalemia ([K⁺]>5.5 mmol/L). (ii) Primary endpoint: Compared to patients with essential hypertension (EH), patients with HA showed hypokalemia and a >10% increase in muscle Na⁺ (Tab. 1). (iii) Secondary endpoints: At stable antihypertensive medication and urine Na⁺ excretion, oral KCl supplementation eliminated the muscle Na⁺ excess observed at baseline and lowered systolic BP by -8.33 (CI: -14.55, -2.12) in normokalemic patients with EH, and by -7.35 (CI: -12.69, -2.01) mmHg in hypokalemic patients with HA (Tab. 1).
Conclusion: Oral KCl supplementation reversed the body Na⁺/K⁺ redistribution disorder in humans. This intervention was feasible, trackable, and efficiently lowered BP at a cost of ≈ 100 SGD per year (≈ 75 USD). On the conservative assumption that 50% of the observed BP-lowering was caused by KCl, its cost per disability-adjusted life year is ≈ 8,500 SGD (≈ 6,500 USD), falling well below commonly cited cost-effectiveness thresholds for Singapore (≈ 75,000 SGD / 60,000 USD).
Trial registration: ClinicalTrials.gov; identifier NCT06569589.