HTN: Potassium (2015)


He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, Dalton RN, Kaski JC, MacGregor GA. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension. 2010; 55: 681-688. 

PubMed ID: 20083724
Study Design:
Randomized Crossover Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
  • To determine the effects of an increase in potassium intake on:
    • Endothelial function
    • BP
    • Pulse wave velocity
    • Left ventricular mass and diastolic function
    • 24-hour urinary albumin and calcium excretion
    • Biochemical markers of bone turnover. 
  • To compare potassium chloride with potassium bicarbonate on their effects on these measurements. 
Inclusion Criteria:
  • Age 18 years to 75 years
  • Sitting SBP of 140mm Hg to 170mm Hg or DBP of 90mm Hg to 105mm Hg and no previous treatment for raised BP.
Exclusion Criteria:
  • Impaired renal function with plasma creatinine higher than 150mcgmol per L
  • Any secondary cause of hypertension
  • Chronic diarrhea
  • History of ulcer disease
  • Baseline plasma potassium higher than 5.0mmol per L
  • Previous stroke
  • Ischemic heart disease, heart failure, diabetes mellitus, malignancy or liver disease
  • Women who were pregnant, breastfeeding or on oral contraceptives.
Description of Study Protocol:


Subjects recruited from Blood Pressure Unit clinic and general practice.


Randomized crossover trial.

Blinding Used



Subjects were randomized to one of three treatments for four weeks each:

  • Placebo
  • Potassium chloride (6.4mmol per capsule) 
  • Potassium bicarbonate (6.4mmol per capsule).

Statistical Analysis

  • Repeated-measures ANOVA for normally distributed variables to examine if a significant difference among three treatments
  • If there is a significant difference, a paired comparison by T-test is done
  • Bonferroni adjustment for multiple comparisons
  • Potential carryover effect by a general linear model
  • For variables not normally distributed, Friedman test was used for comparisons among three study periods and Wilcoxon signed-ranks test for paired comparisons.    
Data Collection Summary:

Timing of Measurements

Baseline before randomization and at the end of each four-week randomized period.

Dependent Variables

  • BP and ambulatory BP monitoring
  • Routine biochemistry, plasma renin activity, aldosterone measured in fasting blood
  • Biochemical markers of bone turnover measured in fasting blood by immunoassay: Procollagen type I N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin and C-terminal cross-linking telopeptide of type I collagen (ßCTX)
  • Urinary electrolytes, creatinine, and albumin excretion measured in two 24-hour urine collections
  • Free pyridinoline and free deoxypyridinoline measured through a two-hour early morning fasted urine sample
  • Endothelial function measured through non-invasive technique of brachial artery flow-mediated dilatation
  • Carotid-femoral pulse wave velocity measured non-invasively using an automated device
  • Transthoracic echocardiography exam measured through Vivid 7 ultrasound.

Independent Variables

  • 10 placebo capsules per day for four weeks
  • 10 potassium (K) bicarbonate capsules per day (6.4mmol K per capsule) for four weeks
  • 10 KCl capsules per day (6.4mmol K per capsule) for four weeks.

Control Variables

  • Usual diet and lifestyle
  • Avoidance of intense physical exercise.


Description of Actual Data Sample:
  • Initial N: N=46 
  • Attrition (final N):  N=42 (30 males, 12 females)
  • Age: Aged 51±10 years
  • Ethnicity: A total of 29 white, 10 black, three Asian
  • Anthropometrics: Subjects served as own control in crossover trial
  • Location: London.


Summary of Results:

Key Findings

  • Increase of 45mmol in 24-hour urine K excretion with KCl and 48mmol with K bicarbonate compared with placebo. There was no significant difference in 24-hour urinary K between KCl and K bicarbonate.
  • Compared with placebo, there was no significant change in office BP with either K. Ambulatory BP monitoring showed a small but significant difference in 24-hour and daytime SBPs among the three treatments. Paired comparison showed that 24-hour and daytime SBPs were slightly lower with KCl vs. K bicarbonate (P=0.057 for 24-hour systolic and P<0.01 for daytime SBPs).
  • Heart rate and body weight did not change with either K treatment
  • Plasma K was slightly higher on KCl (P<0.01) vs. placebo. However, mean plasma K was the same as placebo on K bicarbonate. There were no significant differences among the three treatments for hematocrit or plasma sodium, chloride, bicarbonate, creatinine, albumin, renin activity and aldosterone or 24-hour urinary sodium and creatinine. 
  • Brachial artery diameter was similar among the three treatments. After flow-mediated dilation, the increase in brachial artery diameter was significantly greater with both K treatments vs. placebo, but was not significantly different between the two Ks.
  • Pulse wave velocity showed a significant decrease with both K treatments vs. placebo, but there was no difference between the two
  • Compared with placebo, there was a 24% decrease in albumin excretion with KCl; but no significant change in albumin excretion with K bicarbonate. Urinary albumin:creatinine rate was significantly lower with KCl vs. placebo and K bicarbonate. 
  • Echocardiogram data showed a small but significant difference in LV mass and LV mass index among the three treatments. Compared with placebo, LV mass was significantly lower with KCL (P<0.05) and borderline significant with K bicarbonate (P=0.051) and LV mass index was significantly lower with KCL. LV systolic function did not show any significant change with either K. LV diastolic function was improved significantly with both K treatments. There was no significant difference between K salts in any of the echo measurements. 
  • There was a significant reduction in 24-hour urinary calcium, calcium:creatinine ratio, and plasma ßCTX with K bicarbonate vs. placebo or KCl. There were no significant changes in other bone markers. KCl did not result in a significant change in urinary calcium or any markers of bone turnover vs. placebo. Urinary pH was significantly higher on K bicarbonate vs. placebo and KCl. 


Author Conclusion:
An increase in potassium intake had beneficial effects on the cardiovascular system, and potassium bicarbonate may improve bone health. These effects were found in individuals who already had a relatively low-salt and high-potassium intake. 
Funding Source:
British Heart Foundation
Reviewer Comments:
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes