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Original research article
Effect of low-sodium salt substitutes on blood pressure, detected hypertension, stroke and mortality: A systematic review and meta-analysis of randomised controlled trials
  1. Adrian V Hernandez1,2,
  2. Erin E Emonds1,
  3. Brett A Chen1,
  4. Alfredo J Zavala-Loayza3,
  5. Priyaleela Thota4,
  6. Vinay Pasupuleti5,
  7. Yuani M Roman1,
  8. Antonio Bernabe-Ortiz3,6,
  9. J Jaime Miranda3
  1. 1 University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, Connecticut, USA
  2. 2 School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru
  3. 3 CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
  4. 4 Hemex Health Inc., Portland, Oregon, USA
  5. 5 ProEd Communications Inc., Cleveland, Ohio, USA
  6. 6 London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr Adrian V Hernandez, University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT 06102, USA; adrian.hernandez-diaz{at}


Objective A systematic review and meta-analysis was conducted to assess the efficacy of low-sodium salt substitutes (LSSS) as a potential intervention to reduce cardiovascular (CV) diseases.

Methods Five engines and were searched from inception to May 2018. Randomised controlled trials (RCTs) enrolling adult hypertensive or general populations that compared detected hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), overall mortality, stroke and other CV risk factors in those receiving LSSS versus regular salt were included. Effects were expressed as risk ratios or mean differences (MD) and their 95% CIs. Quality of evidence assessment followed GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology.

Results 21 RCTs (15 in hypertensive (n=2016), 2 in normotensive (n=163) and 4 in mixed populations (n=5224)) were evaluated. LSSS formulations were heterogeneous. Effects were similar across hypertensive, normotensive and mixed populations. LSSS decreased SBP (MD −7.81 mm Hg, 95% CI −9.47 to –6.15, p<0.00001) and DBP (MD −3.96 mm Hg, 95% CI −5.17 to –2.74, p<0.00001) compared with control. Significant increases in urinary potassium (MD 11.46 mmol/day, 95% CI 8.36 to 14.55, p<0.00001) and calcium excretion (MD 2.39 mmol/day, 95% CI 0.52 to 4.26, p=0.01) and decreases in urinary sodium excretion (MD −35.82 mmol/day, 95% CI −57.35 to –14.29, p=0.001) were observed. Differences in detected hypertension, overall mortality, total cholesterol, triglycerides, glucose or BMI were not significant. Quality of evidence was low to very low for most of outcomes.

Conclusions LSSS significantly decreased SBP and DBP. There was no effect for detected hypertension, overall mortality and intermediate outcomes. Large, long-term RCTs are necessary to clarify salt substitute effects on clinical outcomes.

  • hypertension
  • meta-analysis
  • systemic review
  • cardiac risk factors and prevention

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  • Contributor AVH had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AVH and JJM developed the study concept and design. AVH, EEE, BAC, AJZ-L, PT, VP, YMR, AB-O and JJM were involved in data acquisition, analysis or interpretation of the data. AVH, EEE, BAC and VP performed statistical analysis. AVH, VP, EEE, BAC and JJM were involved in drafting of the manuscript. All authors were involved in critical revision of the manuscript for important intellectual content.

  • Funding AVH is supported by the Agency for Healthcare Research and Quality (AHRQ HHSA290201500012I). AB-O (103994/Z/14/Z) and JJM (205177/Z/16/Z) are supported by Wellcome Trust.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This paper has been amended since it was published Online First. The title has been amended to include ‘A systematic review and meta-analysis of randomised controlled trials’.

  • Presented at The abstract of this manuscript was previously published at Journal of the American College of Cardiology 2018;71(11 Suppl): A1749; DOI: 10.1016/S0735-1097(18)32290-3.