Yin X, Rodgers A, Perkovic A, et al. Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis. Heart. 2022 Aug 9. pii: heartjnl-2022-321332. doi: 10.1136/heartjnl-2022-321332. (Systematic review)

OBJECTIVES: The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.

METHODS: We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.

RESULTS: There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was -4.61 mm Hg (95% CI -6.07 to -3.14) and of diastolic blood pressure (DBP) was -1.61 mm Hg (95% CI -2.42 to -0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a -1.53 mm Hg (95% CI -3.02 to -0.03, p=0.045) greater reduction in SBP and a -0.95 mm Hg (95% CI -1.78 to -0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).

CONCLUSIONS: The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.


Discipline Area Score
Internal Medicine 6 / 7
Public Health 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Cardiology 5 / 7
Comments from MORE raters

Cardiology rater

If governments across the globe would advocate evidence-based nutritional guidelines and eliminate unhealthy (processed) foods, >90% of the chronic health problems of the world would go away. Salt substitutes as in this study may be useful, but it does not address the root cause of the problem.

General Internal Medicine-Primary Care(US) rater

Good to know that my recommendations for BP control may have some scientific basis.

General Internal Medicine-Primary Care(US) rater

Blood pressure reductions in those using salt substitutes were associated with clinical outcomes of decreased cardiovascular events.

General Internal Medicine-Primary Care(US) rater

We've known for a while that decreasing Na and increasing K in the diet improves BP and, by inference, that it affects the end organ results of HBP. Now we have evidence that this is true. Practitioners, however, need to be mindful of what meds the patient is taking since we now routinely use meds (ACEi, ARB, dri, mra) that may provoke hyperkalemia if this dietary change is made.

Internal Medicine rater

This systematic review and meta-analysis is timely, and specifically lends further relevance to the SSaSS study. Evidence suggests that only a small fraction of Primary, nephrology, and cardiology physicians counsel “diet and activity” in an actionable way. This study should cause clinicians to advise patients with greater specificity about salt intake and palatable methods to reduce sodium intake.
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