Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease



Low potassium intake can affect cardiovascular disease (CVD) risk and cardiometabolic risk factors.


We hypothesize that potassium chloride (KCl) supplementation can improve cardiovascular risk metabolomic profile.


In this secondary analysis of a pilot randomized clinical trial (RCT) of 26 participants with prediabetes randomized to KCl or placebo, we performed targeted mass-spectrometry-based metabolomic profiling on baseline and 12-week (end-of-study) plasma samples. Principal component analysis (PCA) was used to reduce the many correlated metabolites into fewer, independent factors that retain most of the information in the original data.


Those taking KCl had significant reductions (corresponding to lower cardiovascular risk) in the branched-chain amino acids (BCAA) factor (P = 0.004) and in valine levels (P = 0.02); and non-significant reductions in short-chain acylcarnitines (SCA) factor (P = 0.11).


KCl supplementation may improve circulating BCAA levels, which may reflect improvements in overall cardiometabolic risk profile.

Clinical Trials Registry identifier: NCT02236598;

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Data availability

De-identified data described in the manuscript, code book, and analytic code will be made available upon review of requests.



Hemoglobin A1c


Branched-chain amino acids


Cardiovascular disease


Interquartile range


Potassium chloride


Long-chain acylcarnitines


Oral glucose tolerance test


Principal component analysis


Short-chain acylcarnitines


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We thank the participants who were very much invested in and supportive of the trial and the biorepository, which allowed for this study.


National Institutes of Health/Clinical and Translational Science Award at Duke UL1TR002553 (CAD). National Institutes of Health/Duke Clinical and Translational Science award KL2TR001115-02 (RC); National Institutes of Health/Clinical and Translational Core for the Duke O’Brien Center for Kidney Research, award 1P30DK096493-03 (RC). National Institutes of Health R01-HL127009 (Sha).

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RC, LPS, DD, PHL, DE, SHS designed research (project conception, development of overall research plan, and study oversight); RC, CAD, CS, JJ, OI, LK conducted research (hands-on conduct of the experiments and data collection); OI, LK provided essential reagents or provided essential materials (applies to authors who contributed by providing animals, constructs, databases, etc., necessary for the research); CAD, LK analyzed data or performed statistical analysis; RC, CAD, LK, PHL, CS, JJ, OI, LPS, DD, DE, SHS wrote paper (only authors who made a major contribution); RC, SHS had primary responsibility for final content.

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Correspondence to Ranee Chatterjee.

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Chatterjee, R., Davenport, C.A., Kwee, L. et al. Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease. Metabolomics 16, 75 (2020).

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  • Potassium chloride
  • Potassium supplements
  • Prediabetes
  • Metabolites
  • Branched-chain amino acids
  • Cardiovascular disease risk