The Effects of Sodium and Potassium on Blood Pressure, Vascular Function and Renal Function (KaNa)

Study on the Effects of Sodium and Potassium on Blood Pressure, Vascular Function and Renal Function in Untreated (pre)hypertensive Subjects

To determine the effect of (1) increased sodium intake and (2) increased potassium intake on blood pressure, vascular function and renal function in untreated (pre)hypertensive subjects.

Study Overview

• Status: Completed
• Conditions: Hypertension; Blood Pressure; Vascular Function; Renal Function
• Intervention / Treatment: Dietary supplement: Sodium; Drug: Potassium; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo controlled cross-over feeding study.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Wageningen, Netherlands, 6703 HD
    • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• (Pre)hypertension, defined as office SBP: 130-159 mmHg;
• No use of antihypertensive, lipid-lowering, anticoagulant or other cardiovascular medication;
• Age at start of the ≥ 40 years;

• Apparently healthy:

  • No reported current or previous metabolic diseases
  • No history of cardiovascular diseases
  • No history of renal, liver or thyroid diseases
  • No history of gastrointestinal diseases
  • No diabetes mellitus
  • Fasting laboratory parameters within normal range: renal function (serum creatinine, ureum), liver function (ALAT, ASAT, ɣ-GT) and serum glucose.

Exclusion Criteria:

• Body mass index > 40 kg/m²;
• Smoking
• Secondary hypertension;
• Weight loss or weight gain of 5 kg or more during the last 2 months;
• Usage of non-steroidal anti-inflammatory drugs (aspirin, ibuprofen, naproxen) and not able or willing to stop taking them from at least 4 weeks prior to the study.
• Medical treatment that may affect blood pressure and not able (or willing) to stop taking them;
• Women taking oral contraceptives or estrogen replacement therapy
• Taking nutritional supplements and unwilling to discontinue;
• Women lactating, pregnant or intend to become pregnant during study;
• Reported dietary habits: medically prescribed diet, slimming diet;
• Reported alcohol consumption > 21 units/w (female subjects) or >28 units/w (male subjects);
• Unable or unwilling to consume one meal every workday at the university, or to consume the prescribed study diet for 13 weeks;
• Problems with consuming the supplements or following the study guidelines;
• Unwilling to undergo home or office blood pressure measurements;
• Recent blood donation i.e. 1 month (male subjects) or 2 months (female subjects) prior to the study and planned donation during the study period;
• Reported intense sporting activities > 10 h/w;
• Not agreeing to be informed about unexpected and medically relevant personal test-results
• Participation in another biomedical trial less than 2 months before the start of the study or at the same time;
• No informed consent signed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium; For 4 weeks subjects will consume 3 grams of sodium by the intake of capsules on top of a low-sodium (2 grams of sodium), low-potassium (2 grams of potassium) diet	Dietary supplement: Sodium; Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.
Active Comparator: Potassium; For 4 weeks subjects will consume 3 grams of potassium by the intake of capsules on top of a low-sodium (2 grams of sodium), low-potassium (2 grams of potassium) diet.	Dietary supplement: Sodium; Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.; Drug: Potassium; Potassium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a potassium intake of 3 grams.
Placebo Comparator: Placebo; For 4 weeks subjects will consume placebo capsules (content: cellulose) on top of a low-sodium low-potassium diet	Dietary supplement: Sodium; Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.; Drug: Placebo; Placebo (cellulose, provided by Microz, Geleen, Netherlands): 8 capsules per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endothelium-dependent flow-mediated dilation comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Ultra-sonography (brachial artery) + Picus system	Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Includes: Office BP (Dinamap, 4 consecutive measurements with 2-min intervals) ABPM (Spacelab; 1x24h, at baseline, week 5, week 9, week 13)	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Change in Pulse Wave Velocity comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Device: SphygmoCor (tonometry) Parameters: Pulse Wave Velocity and at baseline, week 5, week 9 and week 13	Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Change in vasomotion comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Device: PeriFlux 5000 (Perimed, Sweden0	Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Change in Biomarkers of endothelial function comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide	Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Change in renal function comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	eGFR, serum creatinine (at screening also used as safety parameter)	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Change in cardiovascular parameters in plasma comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose (at screening also used as safety parameter)	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Liver function parameters	Montoring liver function parameters for safety: includes ALAT, ASAT and ɣ-GT	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
24-hour urinary mineral excretions	Sodium and potassium (as compliance markers)	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
24-hour excretion of protein, albumin and creatinine	In addition, protein is assessed in spot urine during screening using a dipstick test	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Adverse events	Patient diary for occasions of illness, hospitalizations, medication use and other information on potential side effects	Every day
Anthropometric measurements	Body weight (weekly), height (only at baseline), waist circumference (baseline and every 4 weeks)	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Heart rate	Dinamap, 4 consecutive measurements with 2-min intervals	Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)
Food frequency questionnaire		Screening
Change in Pulse Wave Analysis comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake.	Device: SphygmoCor (tonometry)	Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3)

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Top Institute Food and Nutrition
• Investigators: Principal Investigator: Johanna M Geleijnse, PhD, Wageningen University, Division of Human Nutrition

Publications and helpful links

General Publications

• Humalda JK, Yeung SMH, Geleijnse JM, Gijsbers L, Riphagen IJ, Hoorn EJ, Rotmans JI, Vogt L, Navis G, Bakker SJL, de Borst MH. Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study. J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3246-56. doi: 10.1210/clinem/dgaa359.

Helpful Links

• Website of the Top Institute Food and Nutrition, Wageningen, The Netherlands

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: April 9, 2012
• First Posted (Estimated): April 10, 2012

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: blood pressure; potassium; endothelial function; renal function; dietary intervention; flow-mediated dilatation; sodium; salt; controlled feeding study
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: KaNa-trial