Downloaded from https://www.cambridge.org/core British Journal of Nutrition (2008), 99, 1284–1292 doi: 10.1017/S0007114507864853 q The Authors 2007 The effect of a dietary supplement of potassium chloride or potassium citrate . IP address: on blood pressure in predominantly normotensive volunteers 170.106.40.139 Alessandro Braschi and Donald J. Naismith* Department of Nutrition and Dietetics, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK , on 30 Sep 2021 at 17:27:21 (Received 12 May 2007 – Revised 9 October 2007 – Accepted 11 October 2007 – First published online 6 December 2007) Blood pressure (BP) shows a continuous relationship with the risk of CVD. There is substantial evidence that dietary potassium exerts an anti- pressor effect. Most clinical trials have used KCl. However, the chloride ion may have a pressor effect and in foods potassium is associated with organic anions. In a double-blind randomized placebo-controlled trial we explored the effect on BP of two salts of potassium, KCl and pot- , subject to the Cambridge Core terms of use, available at assium citrate (K-cit), in predominantly young healthy normotensive volunteers. The primary outcome was the change in mean arterial pressure as measured in a clinic setting. After 6 weeks of supplementation, compared with the placebo group (n 31), 30 mmol K-cit/d (n 28) changed mean arterial pressure by 25·22 mmHg (95 % CI 28·85, 24·53) which did not differ significantly from that induced by KCl (n 26), 24·70 mmHg (26·56, 22·84). The changes in systolic and diastolic BP were 26·69 (95 % CI 28·85, 24·43) and 24·26 (95 % CI 26·31, 22·21) mmHg with K-cit and 25·24 (95 % CI 27·43, 23·06) and 24·30 (95 % CI 26·39, 22·20) mmHg with KCl, and did not differ significantly between the two treatments. Changes in BP were not related to baseline urinary electrolytes. A greater treatment-related effect was observed in those with higher systolic BP. Increasing dietary potassium could therefore have a significant impact on the progressive rise in BP in the entire population. Blood pressure: Dietary supplementation: Potassium salts: Clinical trials: Human subjects Elevated blood pressure (BP) is the most common risk factor effect of either KCl or potassium citrate (K-cit) with a dose for cardiovascular mortality and morbidity worldwide(1). (30 mmol/d) approximating the current dietary deficit in the Much attention has been given to the role of diet in influencing UK population. https://www.cambridge.org/core/terms BP, in particular to the pressor effect of sodium(2) and more recently to the anti-pressor effect of potassium(3,4) and to the British Journal ofinteraction Nutrition between these two cations(5). Diets rich in fruits and vegetables have been found to exert an anti-pressor Experimental methods effect(6 – 8) which has been attributed in part to their high con- Design of the trial tent of potassium(4,5,7). Most clinical trials on potassium and BP have been performed on a small sample of hypertensive The study, approved by the King’s College Research Ethics subjects, having an intervention period lasting less than 1 Committee, took the form of an 8-week randomized, double- month and using high doses of KCl (60–200 mmol/d)(9,10). blind placebo-controlled trial with parallel arm design of However, there is some evidence that the accompanying oral potassium supplementation (ISRCTN no. 52748737). It . chloride anion is essential in determining the pressor effect was aimed to test the effect on BP of 30 mmol/d of two https://doi.org/10.1017/S0007114507864853 of sodium chloride, as sodium salts of bicarbonate, citrate potassium supplements, KCl and K-cit, and to evaluate the and phosphate have been found to be ineffective in raising possible influence of the accompanying anion. The between- BP(11). Moreover, potassium in plant foods is present in groups difference in increments in mean arterial pressure association with organic anions such as citrate or malate(12) (MAP), as measured by the oscillometric sphygmomanometer, and it has been suggested that chloride per se might have a was the primary outcome. pressor effect(13). The few studies reported using non-chloride Based on data from our previous study(14) and assuming a salts of potassium have provided conflicting results. standard deviation of 5·3 mmHg for MAP, a sample size of We hypothesized that organic salts of potassium lower BP and thirty-five subjects per group was required in order to detect would exert a greater anti-pressor effect than KCl. We therefore a change in clinic MAP of 4·0 mmHg at P,0·05 and 80 % conducted a placebo-controlled randomized double-blind trial power. A greater number of participants was recruited to on healthy volunteers, over a 6-week period, to compare the allow for dropouts. Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; K-cit, potassium citrate; MAP, mean arterial pressure; RBC-K, erythrocyte content of potassium; SBP, systolic blood pressure. * Corresponding author: Professor Donald J. Naismith, fax þ 44 207 333 4285, email [email protected] Downloaded from https://www.cambridge.org/core Potassium supplementation and blood pressure 1285 Volunteers were invited to participate in a 2-week run-in thus avoiding high local concentrations of the salt. Two cap- period during which placebo capsules were taken in order to sules were taken three times a day after each main meal test adherence or intolerance to the placebo (lactose). They (breakfast, lunch and dinner). were also asked, on a voluntary basis, to provide a blood and a 24 h urine sample to obtain baseline values for 24 h elec- . IP address: Blood pressure and heart rate trolyte excretion, plasma electrolytes and erythrocyte potass- ium content (RBC-K). Baseline values for BMI, heart rate BP was measured following current recommendations(15,16) (14) and BP were then measured. Volunteers were randomly allo- as outlined in our previous study . Briefly, BP was assessed 170.106.40.139 cated to receive either a placebo, KCl or K-cit capsules for at approximately the same time of the day (within 30 min) by 6 weeks and were required to attend a final evaluation the same observer using the same instruments throughout the during which heart rate, BP and BMI were again measured study. Participants were asked to maintain the same habits and criteria for exclusion considered. At a mid-term visit BP before each appointment, in particular with regard to factors , on (15) was again measured after 3 weeks of treatment. Three days known to influence BP such as exercise, awakening time 30 Sep 2021 at 17:27:21 from the end of supplementation a second 24 h urine and and meal time. They were asked to refrain from smoking, blood sample were obtained. Volunteers were asked to com- eating, drinking and exercising 30 min before each appoint- plete a questionnaire to determine whether the supplements ment. Those who felt unwell or stressed, or had changes of had side-effects. pulse greater than 15 beats/min when compared with the Adherence to the treatment was calculated as a percentage average baseline pulse were asked to arrange another of assigned capsules actually consumed and confirmed by appointment. , subject to the Cambridge Core terms of use, available at urine analysis. BP was measured in the seated position in the left arm after Randomization was performed by a statistician consultant a 10 min rest using a clinically validated(17) semi-automated unrelated to the intended study using a series of computer-gen- oscillometric sphygmomanometer (UA-779; A & D Instru- erated random numbers (Excel, Office 1997, Microsoft Ltd, ments Ltd, Maidenhead, UK) providing pulse measurements. Reading, UK). Details of the series were unknown to the Three readings were taken at 2 min intervals. The values for investigators and were provided on completion of the study. SBP were then averaged, the reading that had the greatest difference from the mean being discarded together with the corresponding DBP and pulse measurement, and the mean Subjects of the two remaining readings used for analysis. A total of 127 subjects were recruited from amongst the aca- BP was thereafter confirmed by taking two more readings at demic staff and the student population of King’s College 2 min intervals with a validated(18) mercury sphygmoman- London. Ninety completed the study. ometer (Trimline-PyMah; MedRoDi Medical Ltd, Whitecross, Participants had to be aged between 22 and 65 years, have UK). SBP was measured as the point of appearance of the a BMI between 19 and 35 kg/m2, an alcohol consumption Korotkoff sounds (Phase I) while DBP was judged as the of # 21 units/week for women and # 28 units/week for point of complete disappearance of the sounds (Phase V). https://www.cambridge.org/core/terms men (1 unit ¼ 10 ml of ethanol), and have a systolic BP MAP was calculated as (2 DBP þ SBP)/3. Three different (SBP) # 160 and diastolic BP (DBP) # 105 mmHg at screen- cuffs were used depending on arm circumference(15). Partici- British Journal ofing. Nutrition Subjects taking medications for which potassium sup- pants with measurements of either SBP $ 140 or DBP $ 90 plementation is not contraindicated, or mineral and vitamin mmHg were regarded as hypertensive(19). Since oscillometric supplements, took part with the provision that they would monitors may be unreliable for some individuals for which continue their use. None contained potassium. Participants there is no obvious reason(20), those who at screening had a suffering from postural hypotension were also not included.