The progression of evidence of linking high salt intake with cardiovascular conditions has leapfrogged, from studies showing a reduction in consumption associated with lower blood pressure to clinical trials confirming cause-and-effect – and now, a new incentive.
Recent data from a subset of the Salt Substitute and Stroke Study demonstrated that a salt alternative with 25% potassium reduced the risk for recurrent stroke and death.
Investigators of the randomised study led by Xiong Ding, MPH, with the School of Public Health at Wuhan University in China, reported that those reductions came with no greater risk for hyperkalaemia, which has been a safety concern with salt substitutes.
Double-digit percentage improvements
With a 14% reduction in stroke and 12% decrease in death, the simple intervention of salt substitution could significantly improve secondary prevention of stroke and cardiovascular health on a global scale, the investigators reported in JAMA Cardiology.
The US Food and Drug Administration (FDA) says that table salt is not the biggest problem, and 70% of dietary sodium comes from eating packaged and prepared foods. The agency says it is working with the food industry “to make reasonable reductions in sodium across a wide variety of foods”.
In an article accompanying the new trial result, editorialists led by Daniel Jones, MD, with the Department of Medicine at the University of Mississippi Medical Centre, call this “the tipping point” for evidence that lower sodium consumption can improve health.
When sceptics are asked what it would take for mandatory sodium reductions to be enforced, the editorialists point out, the common response is “a clinical trial demonstrating that a reduction in dietary sodium caused a reduction in cardiovascular events”.
The new data, combined with other results, could be the proof needed to move recommendations toward requirements for sodium reduction in foods.
This month, the World Health Organisation released new guidelines recommending reducing sodium intake to less than one teaspoon a day.
Each year, 8m deaths worldwide are linked to poor diet, reports the agency, and 1.9m of those deaths can be attributed to high sodium intake.
So are we reaching an evidence-based tipping point for regulating sodium? Cardiologist Melissa Tracy, MD, a professor at Rush University in Chicago, told Medscape Cardiology, “Definitively, yes.”
Health improvements in reducing sodium have been demonstrated in a number of studies, she said, and the current trial adds significant health benefits in stroke and mortality risk.
“When you start getting into double-digit reductions in stroke, double-digit reductions in major adverse cardiovascular events, major reduction in death,” she said, “that’s huge.”
Since the original Salt Substitute and Stroke Study, published in 2021 in The New England Journal of Medicine, Tracy said she had made a point of telling her patients about the benefits of salt substitutes.
The trial has also shown no adverse events from increasing potassium levels with salt substitutes, she pointed out.
“This has to be a health regulation, just as we got rid of trans fats. Just as we're trying to get colours removed from foods. Patients who have risks, specifically high blood pressure, can’t even eat out without their blood pressure shooting up.”
However, many in the scientific and public health communities have argued that the evidence has been insufficient to warrant new salt reduction strategies – including the use of government regulation to limit sodium intake.
Luke Laffin, MD, a cardiologist with the Cleveland Clinic, said he would welcome government restrictions on the amounts of sodium in foods, but he doesn’t see that happening anytime soon.
While the findings from the subset of this trial add to the evidence, there are still some questions science hasn’t answered yet, added Laffin, who is co-director of the Centre for Blood Pressure Disorders.
There are always going to be concerns about what to substitute sodium with, he said. “In this trial, it’s potassium chloride. It does have potential dangers, particularly in people with kidney disease and other issues.
“I don’t think we’re at a point where the FDA would ever legislate this,” he said, adding that the agency has supported voluntary reduction efforts.
Better education about food
The major sodium studies, including this latest one, have been conducted in countries outside the United States, Laffin observed.
“You have to remember that Asian populations have a much higher amount of sodium in their diets than a typical North American population.”
China has the world's highest consumption of sodium, and the average daily sodium consumption among Chinese adults is more than two teaspoons of salt a day, even though Chinese Dietary Guidelines recommend well under a teaspoon a day.
“Salt reduction is the number one thing we should be talking about to our patients at high cardiovascular risk, particularly those with hypertension,” Laffin said. “But I think it would take more than (the new research findings) to legislate in the US that manufacturers must have low sodium content.”
“Less than about 3% of the average person’s daily sodium intake is from the saltshaker. It’s mostly in the things we’re eating – bread or cheeses or salad dressings. And we know that anything from the deli counter is just jam-packed with sodium.”
Study details
Salt substitution and recurrent stroke and death; a randomised clinical trial
Xiong Ding, Xinyi Zhang, Liping Huang, et al.
Published in JAMA Network on 5 February 2025
Abstract
Importance
The direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear.
Objective
To evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke.
Design, Setting, and Participants
The Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomised clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analysed from November 2023 to August 2024.
Interventions
Participants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt.
Main Outcomes and Measures
The primary outcome was recurrent stroke.
Results
After excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was −2.05 mm Hg (95% CI, −3.03 to −1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on haemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalaemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96).
Conclusions and Relevance
Results of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke.
JAMA editorial – Dietary Sodium- and Potassium-Enriched Salt Substitutes—The Tipping Point?
WHO salt guidelines (Open access)
Medscape article – Is This the Tipping Point to Slash Salt in Our Diet (Open access)
See more from MedicalBrief archives:
Salt substitutes slash risk of CVD, death – Chinese-Australian meta-analysis
Sodium content policy change can save 7m lives – WHO
Contentious study shows reduced salt consumption not necessary for cardiac health