Comparative effects of salt substitutes on blood pressure, cardiovascular events and mortality: a systematic review and network meta-analysis

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease. Salt substitutes may reduce sodium intake while maintaining palatability, but comparative effects across formulations remain uncertain. METHODS: We conducted a systematic review and frequentist random-effects network meta-analysis of randomised controlled trials in adults comparing salt substitutes with regular salt, other substitutes or no intervention. Databases (PubMed, Embase, CENTRAL, CNKI, Wanfang), WHO-ICTRP and ClinicalTrials.gov were searched from inception to Oct 3, 2025 (PROSPERO CRD42023451859). We assessed the risk of bias using a modified Cochrane tool and conducted a random-effects network meta-analysis, with evidence certainty evaluated through the GRADE approach. RESULTS: We included 34 randomised controlled trials involving 37,063 participants across 15 countries (17 from China, 17 from other countries; mean age 62.3 years). Our results indicate that moderate-potassium and low-sodium salt substitutes (25-40% KCl, 60-79% NaCl) probably reduce all-cause mortality, cardiovascular mortality, non-fatal cardiovascular events and systolic blood pressure (SBP) compared to regular salt, with reductions of 7-17 deaths per 1000 individuals and 4.39-4.64 mmHg for SBP, based on moderate to high certainty evidence. Mortality and cardiovascular benefits are predominantly driven by one large Chinese trial (SSaSS, n = 20,995); excluding this trial eliminated statistical significance for all-cause mortality. Among non-Chinese studies, none contributed mortality data. Substitutes with higher potassium or very low sodium showed similar blood pressure reductions but provided less certain evidence regarding mortality and events. No substitute increased adverse events or withdrawals, and acceptability was comparable to regular salt. CONCLUSIONS: Salt substitutes, particularly moderate-potassium and low-sodium formulations, represent a promising sodium reduction strategy. However, current evidence for mortality and cardiovascular event benefits is dominated by one large Chinese trial and has very limited generalisability beyond Chinese populations with high discretionary salt use. These products appear acceptable and safe in people without renal impairment, but clinicians should rule out kidney disease and hyperkalaemia risk before recommending them, and large trials in non-Chinese populations are needed.