Hypertension, Blood Pressure, Vascular Function, Renal Function
Conditions
Keywords
sodium, salt, potassium, blood pressure, flow-mediated dilatation, endothelial function, renal function, controlled feeding study, dietary intervention
Brief summary
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.
Detailed description
This is a randomized, double-blind, placebo controlled cross-over feeding study.
Interventions
DIETARY_SUPPLEMENTSodium
Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.
DRUGPotassium
Potassium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a potassium intake of 3 grams.
DRUGPlacebo
Placebo (cellulose, provided by Microz, Geleen, Netherlands): 8 capsules per day.
Sponsors
Wageningen University
Top Institute Food and Nutrition
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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) | Ultra-sonography (brachial artery) + Picus system |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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) | Device: SphygmoCor (tonometry) Parameters: Pulse Wave Velocity and at baseline, week 5, week 9 and week 13 |
| Change in vasomotion comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | 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) | Device: PeriFlux 5000 (Perimed, Sweden0 |
| 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. | 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) | 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 |
| Change in renal function comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | 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) | eGFR, serum creatinine (at screening also used as safety parameter) |
| 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. | 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) | Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose (at screening also used as safety parameter) |
| Liver function parameters | 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) | Montoring liver function parameters for safety: includes ALAT, ASAT and ɣ-GT |
| Change in blood pressure comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | 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) | Includes: Office BP (Dinamap, 4 consecutive measurements with 2-min intervals) ABPM (Spacelab; 1x24h, at baseline, week 5, week 9, week 13) |
| 24-hour excretion of protein, albumin and creatinine | 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) | In addition, protein is assessed in spot urine during screening using a dipstick test |
| Adverse events | Every day | Patient diary for occasions of illness, hospitalizations, medication use and other information on potential side effects |
| Anthropometric measurements | 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) | Body weight (weekly), height (only at baseline), waist circumference (baseline and every 4 weeks) |
| Heart rate | 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) | Dinamap, 4 consecutive measurements with 2-min intervals |
| 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. | 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) | Device: SphygmoCor (tonometry) |
| 24-hour urinary mineral excretions | 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) | Sodium and potassium (as compliance markers) |
Countries
Netherlands
Outcome results
None listed