• In adults, using LSSS instead of regular salt in food probably lowers blood pressure slightly. Adults using LSSS instead of regular salt probably have a slightly lower risk of non-fatal heart conditions, such as stroke or a sudden reduced blood flow to the heart, and death from heart disease.
• Using LSSS instead of regular salt probably also slightly increases the level of blood potassium (a mineral that keeps your heart beating at the right pace) in adults. This could be harmful for people who cannot effectively regulate the potassium in their bodies. Other evidence on safety is very limited.
• We are not certain about effects of using LSSS instead of regular salt on blood pressure in children, or whether using LSSS is safe in children.
• This evidence may not directly apply to people known to be at risk of high blood potassium, such as people with kidney problems or on certain medications.
What are low-sodium salt substitutes (LSSS)?
LSSS are products with less sodium than regular salt. Amounts of sodium in LSSS are lowered by replacing some of the sodium with potassium or other minerals. LSSS may help lower risks of using regular salt, since eating lots of sodium and not enough potassium contributes to high blood pressure. Globally, high blood pressure is the largest cause of preventable deaths, mainly because it causes stroke, acute coronary syndrome (ACS; where less blood flows to the heart), and kidney problems.
However, LSSS also has potential health risks. Using LSSS may lead to higher than normal blood potassium (hyperkalaemia), which causes problems with the heartbeat speed and rhythm, or can cause the heart to stop. These risks are greater in certain people, for example, those whose kidneys do not work properly to remove potassium.
What did we want to find out?
We wanted to find out what the effects of using LSSS instead of regular salt are on blood pressure as well as on events (stroke and ACS) and heart disease death. We also wanted to know if using LSSS instead of regular salt is safe, both in the general population and in people who are known to be at risk of high blood potassium levels.
We wanted to find this out for adults, children and pregnant women.
What did we do?
We searched five electronic databases and trial registries for studies that compared using LSSS with using regular salt. We compared and summarised the results of the studies and rated our confidence in the combined evidence, based on factors such as study methods and sizes.
What did we find?
We found 26 trials* involving 34,961 adults and 92 children. No studies in pregnant women were found. Most trials were undertaken in rural or suburban areas, with more than half done in low- and middle-income countries. Most trials included some people with high blood pressure (22); the largest included only people with a high risk of stroke. Seven trials were done in people at possible risk of high blood potassium. All trials excluded people where high potassium intake is known to be harmful, such as people with kidney problems or on certain medications. Nearly all trials (23) examined LSSS types where some sodium was replaced with potassium. The amount of sodium replaced in the various LSSS used in the trials ranged from very small (3%) to large (77%).
*Trials are types of studies in which participants are assigned randomly to two or more treatment groups. This is the best way to ensure similar groups of participants.
In adults, LSSS probably lowers blood pressure (diastolic and systolic) slightly when compared to regular salt. Using LSSS also probably lowers risk of non-fatal stroke, non-fatal ACS and heart disease death slightly when compared to regular salt.
However, using LSSS instead of regular salt probably also slightly increases the level of potassium in the blood.
Compared to regular salt, LSSS may result in little to no difference in high blood pressure and hyperkalaemia.
We could not draw any conclusions about effects of LSSS on blood pressure control, various heart disease events, death caused by stroke, lower than normal blood potassium (hypokalaemia), and other adverse events.
We could not draw any conclusions about the effects or safety of using LSSS instead of regular salt in children.
What are the limitations of the evidence?
We are moderately confident in the evidence. Our confidence was lowered mainly because of concerns about how some trials were conducted, and whether the results apply to the general population. We are not sure about the effects and safety of LSSS in children, pregnant women, people known to have a risk of high blood potassium, or those who do not have high blood pressure. We are also unsure about the effects of LSSS when used in foods not prepared at home. Further research may change these results.
How up to date is this evidence?
The evidence is up-to-date to August 2021.
When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.
Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake. Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion.
To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children.
We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied.
We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration.
Two review authors independently screened titles, abstracts and full‐text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia.
We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries.
The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years.
We assessed the overall risk of bias as high in six trials and unclear in 12 trials.
LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly.
On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt.
LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence).
LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children.