HTN: Calcium (2015)


Pikilidou, MI, Befani CD, Sarafidis PA, Nilsson PM, Koliakos GG, Tziolas IM, Kazakos KA, Yovos JG, Lasaridis AN. Oral calcium supplementation ambulatory blood pressure and relation to changes in intracellular ions and sodium-hydrogen exchange. Am J Hypertens. 2009; 22: 1,263-1,269.

PubMed ID: 19779467
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  • To evaluate the 24-hour blood pressure change after calcium supplementation
  • To investigate its relation to changes in intracellular cationic concentrations of calcium, magnesium, potassium and sodium and in the activity of the first isoform of sodium-hydrogen exchange in subjects with newly diagnosed hypertension and type 2 diabetes.
Inclusion Criteria:
  • Essential hypertension and type 2 diabetes under treatment with glibenclamide, recruited through the Hypertension and Diabetes Clinic
  • Newly diagnosed with hypertension Stage 1 using the threshold of 130/80mm Hg.
Exclusion Criteria:
Subjects not able to participate in the study's tests.
Description of Study Protocol:


A total of 34 current patients of the Hypertension and Diabetes Clinic were recruited to participate in the study.


Parallel, randomized controlled study, single-blinded with all subjects submitting to all tests and maintaining a low-calcium dietary intake during the study.

Blinding Used

Laboratory personnel testing subjects were blinded to their assignment.


  • Run-in period (4 weeks): Low calcium diet (approximately 500mg per day)
  • Randomization to intervention phase (eight weeks):
    • Test subjects consumed 1,500mg elemental calcium during the eight weeks of the study
    • Control subjects took nothing.

Statistical Analysis

  • Statistical Package for Social Sciences version 13.0 software (SPSS, Chicago, IL) incorporating:
    • Mean
    • Student's T-test with Bonferroni's correction
    • Pearson's (r) product formula
    • Multivariate linear regression analysis
  • P<0.05 was considered statistically significant.
Data Collection Summary:

Timing of Measurements

Baseline and at the end of eight-week study period.

Dependent Variables

  • Ambulatory blood pressure (monitored with Spacelabs 90217 device, Spacelabs Medical, Redmond, WA) measured for 25 hours (discarding the first hour), three times per hour between 8:00 a.m. and midnight, and hourly between midnight and 8:00 a.m. (mm Hg)
  • Intraplatelet magnesium (mcgmol per L)
  • Intraplately calcium (nmol per L)
  • Measurement of NHE-1 activity (mmol per L red cell per hour)
  • Intraerythrocyte sodium (mmol per L)
  • Intraerythrocyte potassium (mmol per L)
  • Totals for 24-hour calcium, magnesium, sodium and potassium.

Independent Variables

Comparing of 1,500mg elemental calcium vs. no supplement.

Control Variables

Change in BMI.

Description of Actual Data Sample:
  • Initial N: N=34
  • Attrition (final N): N=31 (12 male, 19 female)
  • Age: 58.4±6.8 and 59.7±9.0 in calcium and control groups, respectively
  • Ethnicity: Not specified, but authors are affiliated with Greece and Sweden
  • Anthropometrics: BMI, duration of diabetes, weight and waist circumference were all similar between groups
  • Location: Greece or Sweden.


Summary of Results:

Key Findings

  • Calcium supplementation did not result in significant change in mean ambulatory systolic blood pressure, diastolic blood pressure or pulse pressure
  • Calcium supplementation did have significant impact on intra-platelet levels of calcium (decreased, P=0.04), magnesium (increased, P=0.001), intra-erythrocyte potassium (increased, P=0.03) and NHE-1 activity (decreased, P=0.009). See Table 3 of the article for actual amounts.
Author Conclusion:
The authors conclude that they did not find a significant associations of calcium supplementation with 24-hour blood pressure in hypertensive subjects with diabetes. However, there appears an indication of interrelation of calcium levels and NHE-1 activity on blood pressure in patients with hypertension and type 2 diabetes.
Funding Source:
University/Hospital: Aristotle University of Thessaloniki, Malmo University Hospital, Lund University
Reviewer Comments:
  • This is not a dietary intervention.
  • The authors note that the number of subjects and statistical power was low. A sample size of 350 patients would probably show a statistically significant reduction in 24-hour blood pressure (power 80%). A sample size of 79 patients would probably show a significant difference for night-time systolic blood pressure (power 80%).


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? No
  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.) Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? Yes
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  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? Yes
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? No
  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? Yes
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? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  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? Yes
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? Yes
  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)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? Yes
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? ???
  10.2. Was the study free from apparent conflict of interest? Yes