Subjects were recruited via announcements in the local newspapers and from the volunteer register of Oy Foodfiles Ltd in the Kuopio area, Eastern Finland. A written consent form was obtained from each subject. Subjects were eligible if they were between 25-75 years old, with their SBP in the range of 130-159 mmHg and/or DBP in the range of 85-99 mmHg, BMI between 23 and 40 kg/m2 and a stable body weight. Subjects were excluded if they were taking antihypertensive drugs, non-steroidal anti-inflammatory agents, cyclosporine or tacrolimus. They were also excluded if they had secondary hypertension, diabetes (type 1 or 2), a history of active heart disease or cancer, abnormal electrolytes, proteinuria, abnormal liver, kidney or thyroid function. Subjects were also excluded if they were currently on a low-salt diet (six or less points in the salt intake test by the Finnish Heart Association, Helsinki). Subjects with alcohol abuse (> 14 units per week) or drug abuse were excluded. Pregnant and lactating mothers were also excluded.
Study products and diets
The test product was Smart Salt® SMS50 supplied by Smart Salt® Inc (California USA). Smart Salt® contained 50% sodium chloride (NaCl), 25% potassium chloride (KCl) and 25% magnesal; magnesium ammonium potassium chloride, hydrate [Mg4K(NH4)3Cl12·24H2O]. The control was a regular salt (sodium chloride, NaCl) (Akzo Nobel Salt, Netherlands).
During the treatment period, the main food sources of salt were either salted as normal or with Smart Salt®, depending on the study group. Test foods were industrially processed main dishes (casseroles, soups, pastas, pizza and minced meat dishes), bread (70% rye bread and 30% multigrain), frankfurters sausage/cold cuts and Edam cheese. Salt used for cooking and baking as well as table salt was either regular salt or Smart Salt®, dependent on group.
The daily amount of the test foods in the study diet was based on national dietary data in Finland, namely the FinDiet 2007 study. In the test group, the NaCl reduction was designed to be 3.1 to 5.6 grams (1.2 to 2.2 grams Na+) depending on the energy intake and habitual diet of the study subject. The goal was to replace approximately 60% of the regular sources of sodium with Smart Salt products in the intervention group. The daily sodium intake in the Regular Salt group was designed to stay at the same level as typical for that individual. The amounts of Smart Salt and Regular Salt in recipes of test foods were the same. The analyzed concentration of sodium (expressed as NaCl) in the test foods varied between 0.38-1.41% in Smart Salt foods and 0.64-2.03% in Regular salt foods depending on the food matrix.
All study subjects were told by a nutritionist to refrain from salt-rich products (such as salty snacks, soy sauce, olives, salt-rich cheeses, stock cubes, salty and smoked fish etc.). The use of products containing bioactive peptides (like Evolus®), salts other than the test salts, licorice (Radix glycyrrhizae), ammonium chloride products and any food supplements that might affect BP were also prohibited. Study subjects could freely consume liquid dairy products, vegetables, fruits and berries in addition to the study foods.
Blood pressure and heart rate measurements
BP and heart rate were measured using an automatic sphygmomanometer (Omron M4-I, fully automatic BP monitor, Omron Matsusaka Co, Ltd, Japan) following 10 minutes rest in a sitting position. BP was measured three times with intervals of at least two minutes, between the hours of 7:00 am and 12:00 noon. The mean of the last two BP measurements was used as the result. BP was measured using the non-dominant arm with the exception of the first study visit during which BP was measured using both arms. If the BP in the two arms differed in SBP or DBP by more than 10 mmHg, the arm with the higher reading was used for all subsequent measurements. Volunteers were not told the results of their BP measurements during the study and the study nurse was unaware of the treatment allocations.
Weight and height measurements
Body weight was measured using a calibrated digital scale (Scale Seca 704, Medical scales and measuring systems Seca GmbH & Co, Germany). Height was measured with a Seca telescoping measuring rod type 221 (Vogel & Halke GmbH & Co, Germany) to the nearest crossed half a centimeter at the first study visit (-4 wk). Body mass index (BMI) was calculated with the equation: weight (kg)/height (m)2.
24-hour urine collection
The subjects completed 24 hour urine collections twice during the study; before the intervention period (-1 day) and once at end of the intervention period (+8 wk). Urine collections were required to account for a minimum of 20 hours and a maximum of 28 hours, with the amount lost being ≤ 10% of total urine. Urine samples were analyzed for sodium, potassium, magnesium and creatinine at the ISLAB laboratories, Kuopio. Urinary creatinine was analyzed using an enzymatic method. Urinary potassium and sodium were measured using an ion-specific electrode (ISE). Magnesium was measured using atomic absorption spectrometry. The completeness of urine excretion was checked in the present study by calculating the sodium excretion in relation to 24-hour creatinine excretion.
Blood samples were taken after a 10 to 12 hour overnight fasting period and after BP had been measured. Blood samples were analyzed using standardized methods of hematology and clinical chemistry at the ISLAB laboratories, Kuopio. Plasma sodium and potassium were analyzed by ion-specific electrode and plasma magnesium was analyzed using atomic absorption spectrometry.
The compliance of the test protocol was assured using individual diaries in which the use of test products was recorded. The subjects also recorded in their daily diary their weight, any possible adverse effects, changes in lifestyle and medications during the study.
Data management and statistical analysis
Data management and analyses were performed using SPSS (version 17.0, SPSS Inc, Chicago, USA). The results are presented as means and standard deviations. The normal distribution of variables was checked using the Shapiro-Wilk test. The equality of variances among the study groups was tested using the Levene test. The equality of variance-covariance matrices across cells was tested using the Box's M test. The general linear model (GLM) for repeated measures was used to test between-groups and with-in group differences using repeated continuous variables. In the event of a significant time/group interaction, independent sample t-tests were conducted using the Bonferroni correction in among-group analyses and comparisons within groups were conducted using paired sample t-tests. For the continuous variables, which were not normally distributed even after logarithmic transformation, the Mann-Whitney test (among groups) and Wilcoxon test or Friedman test (with-in group) were conducted with Bonferroni correction when applicable. P-values less than 0.05 were regarded as statistically significant.