Salt Substitutes Lower BP, Reduce Risk of Cardiovascular, All-cause Mortality Across Patients, Borders

Meta-analysis authors say the significant preventive effects of replacing use of salt with salt substitutes have important worldwide public health implications.

Use of salt substitutes was linked to declines in blood pressure and to reduced risk of cardiovascular and all-cause mortality in a meta-analysis including nearly 32 000 participants.

The team reporting the results, comprised of investigators from the recent landmark Salt Substitute and Stroke Study (SSaSS), says their new findings apply broadly across population subgroups and geographies, augmenting and expanding the SSaSS results and suggesting implications for public health policy.

The systematic review and meta-analysis was led by Bruce Neal, MBChB, PhD, of the George Institute for Global Health, at the University of New South Wales, in Australia, who was also the lead investigator for the SSaSS. The SSaSS found that replacing regular salt with a reduced sodium potassium fortified salt substitute reduced risk of stroke, MACE, and premature mortality among adults with previous stroke or uncontrolled hypertension living across rural China.

With this current systematic review and meta-analysis, Neal and colleagues sought to broaden understanding of the effects of the salt substitute on additional outcomes, to quantify the consistency of the SSaSS findings, and to explore applicability of their findings beyond the original study population.

The team searched PubMed, Embase and Cochrane Library databases from inception through August 31, 2021, for all parallel-group, step-wedged, or cluster randomized controlled trials that evaluated the impact of salt substitutes on blood pressure or clinical outcomes.

The search returned 21 trials (N=31 939) of which 19 reported effects on blood pressure and 5 reported effects on clinical outcomes. To define the consistency of the different findings across trials, location, and patient subgroups, Neal et al report using meta-analyses and meta-regressions.


The team found that use of a salt substitute was associated with an overall reduction of systolic blood pressure (SBP) of -4.61 mmHg (95% CI, -6.07 to -3.12) and of diastolic blood pressure (DBP) of -1.61 mmHg (95% CI, -2.42 to -0.79). The observed decreases appeared to be consistent, the investigators write, across geographical regions and across 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 excretion (all for homogeneity >.05).

After applying metaregression, Neal and colleagues found that for each 10% lower proportion of sodium chloride in the salt substitute used there was an associated -1.53 mmHg (95% CI, -3.02 to -0.03; P=.045) greater reduction in SBP and a -0.95 mmHg (95% CI,-1.78 to-0.12; P=.025) greater reduction in DBP.

The investigators also observed “clear protective effects” of salt substitute use on total mortality (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]). Overall, they add, there were no serious adverse events attributable to hyperkalemia across studies.

“Since blood pressure lowering is the mechanism by which salt substitutes confer their cardiovascular protection, the observed consistent blood pressure reductions make a strong case for generalisability of the cardiovascular protective effect observed in SSaSS both outside of China and beyond the SSaSS population,” the investigators conclude.

They add that the findings support the adoption of salt substitutes at the individual level, ie in clinical practice, and as integral to public health policy “as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure and prevent major cardiovascular events.”

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