Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials.

JAMA, 277(20):1624-32 1997 May 28

OBJECTIVE: To assess the effects of supplementation with oral potassium on blood pressure in humans. DESIGN: Meta-analysis of randomized controlled trials. DATA SOURCES: English-language articles published before July 1995. STUDY SELECTION: Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. DATA EXTRACTION: Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. RESULTS: By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of -3.11 mm Hg (-1.91 to -4.31 mm Hg) and -1.97 mm Hg (-0.52 to -3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. CONCLUSIONS: Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.

Antiarrhythmic effects of increasing the daily intake of magnesium and potassium in patients with frequent ventricular arrhythmias. Magnesium in Cardiac Arrhythmias (MAGICA) Investigators.

J Am Coll Cardiol, 29(5):1028-34 1997 Apr

OBJECTIVES: This study sought to assess potential antiarrhythmic effects of an increase in the daily oral intake of magnesium and potassium in patients with frequent ventricular arrhythmias. BACKGROUND: Magnesium and potassium contribute essentially to the electrical stability of the heart. Despite experimental and clinical evidence for the antiarrhythmic properties of the two minerals, controlled data in patients with stable ventricular arrhythmias are lacking. METHODS: In a randomized, double-blind study, 232 patients with frequent ventricular arrhythmias ( 720 ventricular premature beats [VPBs]/24 h) confirmed at baseline and after 1 week of placebo therapy were subsequently treated over 3 weeks with either 6 mmol of magnesium/12 mmol of potassium-DL-hydrogenaspartate daily or placebo. RESULTS: Compared with placebo pretreatment, active therapy resulted in a median reduction of VPBs by -17.4% (p = 0.001); the suppression rate was 2.4 times greater than that in patients randomized to 3 weeks of placebo therapy (-7.4%, p = 0.038). The likelihood of a or = 60% (predefined criterion) or or = 70% suppression rate (calculated from the placebo-controlled run-in period) was 1.7 (25% vs. 15%, p = 0.044) and 1.5 times greater in the active than in the placebo group (20% vs. 13%, p = 0.085), respectively. No effect of magnesium and potassium administration was observed on the incidence of repetitive and supraventricular arrhythmias and clinical symptoms of the patients. CONCLUSIONS: To our knowledge, this study is the first to provide controlled data on the antiarrhythmic effect of oral administration of magnesium and potassium salts when directed to patients with frequent and stable ventricular tachyarrhythmias. A 50% increase in the recommended minimum daily dietary intake of the two minerals for 3 weeks results in a moderate but significant antiarrhythmic effect. However, with the given therapeutic regimen, repetitive tachyarrhythmias and patient symptoms remain unchanged.

Effect of potassium supplementation on blood pressure in African Americans on a low-potassium diet. A randomized, double-blind, placebo-controlled trial.

Arch Intern Med, 156(1):61-7 1996 Jan 8

OBJECTIVE: To determine the effect of potassium supplementation on blood pressure in African Americans consuming a low-potassium diet. DESIGN: Randomized, double-blind, placebo-controlled trial with two parallel arms. SETTING: Community-based research site. PARTICIPANTS: Eighty-seven healthy African Americans aged 27 to 65 years with a systolic blood pressure between 100 and 159 mm Hg and a diastolic blood pressure between 70 and 94 mm Hg. INTERVENTION: During the 21-day intervention period, all participants were provided with a low-potassium diet (32 to 35 mmol/d). In addition to this diet, they were randomly assigned to receive either potassium supplements (80 mmol/d) or placebo. MAIN OUTCOME MEASURE: Change in blood pressure in the potassium vs the placebo group, based on a total of nine blood pressure readings at three visits. Blood pressures were taken before and during the intervention by means of random-zero sphygmomanometry. RESULTS: At baseline, the placebo and potassium groups were similar for mean blood pressure (127/78 vs 125/77 mm Hg), 24-hour urinary potassium excretion (50 vs 44 mmol), and all other variables measured (all P .05). During the intervention, the net difference in 24-hour urinary potassium excretion between groups was 70 mmol. Compared with the placebo group, the potassium supplementation group experienced a net decline in systolic blood pressure of 6.9 mm Hg (95% confidence interval, -9.3 to -4.4 mm Hg; P < .001) and a decline in diastolic blood pressure of 2.5 mm Hg (95% confidence interval, -4.3 to -0.8 mm Hg; P = .004). Simultaneous adjustment for differences in baseline characteristics only strengthened these estimates. CONCLUSIONS: Potassium supplementation reduces blood pressure substantially in African Americans consuming a diet low in potassium. Increased potassium intake may play an important role in reducing blood pressure in this population at high risk for hypertension.

Non-potassium-sparing diuretics and risk of sudden cardiac death.

J Hypertens, 113(2):1539-45 1995 Dec

OBJECTIVE: To review current evidence for a possible association between the use of non-potassium-sparing diuretics and the risk of sudden cardiac death in hypertension. METHODS: Examination of published randomized trials and recent case-control studies. RESULTS: Numerous studies have shown that the administration of non-potassium-sparing diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between diuretics and sudden death. Published randomized trials on the efficacy of non-potassium-sparing diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including potassium-sparing diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-potassium-sparing diuretics had approximately double the risk of sudden cardiac death compared with users of potassium-sparing diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. CONCLUSIONS: Current evidence supports the hypothesis that diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide diuretics at a low dose only. Adding a potassium-sparing diuretic drug may further reduce the mortality risk.

Safety, tolerability, and efficacy of a glucose-insulin-potassium-magnesium-carnitine solution in acute myocardial infarction.

Am J Cardiol, 78(4):477-9 1996 Aug 15

Fifty-four patients with AMI were treated with a front-loaded 15-hour infusion of hypertonic glucose, insulin, potassium, magnesium, and L-carnitine in addition to usual therapy. This metabolic solution was well tolerated, free of serious side effects, and reduced the incidence of morbid events.

Long-term potassium supplementation lowers blood pressure in elderly hypertensive subjects.

Int J Clin Pract, 51(4):219-22 1997 Jun

Following a randomised cross-over trial of the effect of a four-week 60 mmol/day potassium supplement versus placebo on blood pressure (BP), eight of the original 18 hypertensive subjects continued with a 48 mmol daily potassium supplement for four months. For these eight subjects 24-h potassium excretion during placebo, one month of 60 mmol and four months of 48 mmol daily potassium supplementation phases was 56 +/- 23, 102 +/- 28 and 90 +/- 35 mmol/24 hours, respectively, and mean 24-h BP following each phase was 160 +/- 16/89 +/- 11, 147 +/- 13/83 +/- 12 and 145 +/- 14/81+/- 9 mmHg respectively, a significant fall in mean 24-h SBP between four months of potassium supplement and placebo period of 15 +/- 13 mmHg (95% CI: 4, 26 mmHg, p = 0.02), although the fall in 24-h DBP was not significant (8 +/- 11 mmHg, 95% CI: 0, 17 mmHg, p = 0.08). Modest increases in dietary potassium intake could have significant effects on lowering BP in the large proportion of elderly subjects with hypertension.

The effects of potassium depletion and supplementation on blood pressure: a clinical review.

Am J Med Sci, 314(1):37-40 1997 Jul

Nonpharmacologic treatment currently is recognized as an important part in the treatment of hypertension, and the role of dietary potassium intake in blood pressure (BP) control is becoming quite evident. Clinical studies have examined the mechanism by which hypokalemia can increase BP and the benefit of a large potassium intake on BP control. Epidemiologic data suggest that potassium intake and BP are correlated inversely. In normotensive subjects, those who are salt sensitive or who have a family history of hypertension appear to benefit most from the hypotensive effects of potassium supplementation. The greatest hypotensive effect of potassium supplementation occurs in patients with severe hypertension. This effect is pronounced with prolonged potassium supplementation. The antihypertensive effect of increased potassium intake appears to be mediated by several factors, which include enhancing natriuresis, modulating baroreflex sensitivity, direct vasodilation, or lowering cardiovascular reactivity to norepinephrine or angiotensin II. Potassium repletion in patients with diuretic-induced hypokalemia improves BP control. An increase in potassium intake should be included in the nonpharmacologic management of patients with uncomplicated hypertension.

Effects of magnesium and potassium on Wolff-Parkinson-White syndrome.

J Electrocardiol, 29(1):11-5 1996 Jan

To investigate the effects of electrolytes on anterograde conduction via accessory pathways, 12 patients with Wolff-Parkinson-White syndrome received, while in sinus rhythm, intravenous KCl (7 mEq in 200 mL of 0.9% NaCl), MgSO4 (10 mL 20% in 200 mL of 0.9% NaCl), NaCl (0.9%, 200 mL), and procainamide (maximal dose, 10 mg/kg of body weight over a 5-minute period) in a randomized fashion. NaCl had no effect on preexcitation. Procainamide abolished preexcitation in seven patients, of whom five had a similar response with MgSO4 and four with KCl. The finding that potassium and magnesium transiently abolish preexcitation in some Wolff-Parkinson-White patients deserves further study, especially during tachyarrhythmias in patients with accessory pathways.

Normalization of acquired QT prolongation in humans by intravenous potassium.

Circulation, 96(7):2149-54 1997 Oct 7

BACKGROUND: QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as I(Kr) or I(Kl) when extracellular potassium concentration ([K+]o) is increased. Furthermore, increasing [K+]o decreases the potency of I(Kr)-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K+]o corrects QT abnormalities in CHF and in subjects treated with quinidine. METHODS AND RESULTS: KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K+] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTUc prolongation, especially in the precordial leads (quinidine, 590+/-79 to 479+/-35 [+/-SD] ms(1/2), P <.001; CHF, 521+/-110 to 431+/-47 ms(1/2), P<.05). There was no effect in either control group. Similarly, potassium decreased QTUc dispersion (quinidine, 210+/-62 to 130+/-75 ms(1/2), P<.01; CHF, 132+/-68 to 84+/-35 ms(1/2), P=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium. CONCLUSIONS: Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.

Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis.

J Urol, 158(6):2069-73 1997 Dec

PURPOSE: We examined the efficacy of potassium-magnesium citrate in preventing recurrent calcium oxalate kidney calculi. MATERIALS AND METHODS: We conducted a prospective double-blind study of 64 patients who were randomly assigned to receive placebo or potassium-magnesium citrate (42 mEq. potassium, 21 mEq. magnesium, and 63 mEq. citrate) daily for up to 3 years. RESULTS. New calculi formed in 63.6% of subjects receiving placebo and in 12.9% of subjects receiving potassium-magnesium citrate. When compared with placebo, the relative risk of treatment failure for potassium-magnesium citrate was 0.16 (95% confidence interval 0.05 to 0.46). Potassium-magnesium citrate had a statistically significant effect (relative risk 0.10, 95% confidence interval 0.03 to 0.36) even after adjustment for possible confounders, including age, pretreatment calculous event rate and urinary biochemical abnormalities. CONCLUSIONS: Potassium-magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%.

Effect of treatment with magnesium and potassium on mortality and reinfarction rate of patients with suspected acute myocardial infarction.

Int J Clin Pharmacol Ther, 34(5):219-25 1996 May

The aim of the study was to test whether magnesium and potassium administration can decrease both early and late cardiac event rates in 355 patients with suspected acute myocardial infarction (AMI). The study was conducted by a primary and secondary care research centre as a randomized, initially double-blind comparison for 4 weeks followed by a single blind period for 2 years. Patients with definite or possible AMI and unstable angina based on World Health Organization criteria were assigned within 24 hours of infarction to different groups. Treatment was administered for 3 days through intravenous infusion with either 8.12 mmol/day Mg (group A, n = 81), 10.49 mmol/day K (group B, n = 77) 10% dextrose solution (group C, n = 87) or a placebo containing 2% dextrose solution (group D, n = 81). After discharge from the hospital all groups were advised to follow a fat-reduced diet. Groups A, B, and C were also advised to take magnesium hydroxide or potassium chloride orally. Comparison of groups A and B with group D over 2 years indicated that treatment with magnesium or potassium was associated with increased (p < 0.05) serum magnesium and potassium, and significant reduction in the incidence of cardiac events (22 and 24 vs 41 patients), total mortality (9 and 10 vs 20 deaths), and ventricular ectopics (17 and 21 vs 44), respectively, in the groups. Group C showed no significant benefit. It is possible that magnesium and potassium infusion immediately after AMI and addition of Mg and K salts to the AMI regimen may enhance tissue levels of these cations, leading to significant reduction in complications and mortality after 2 years.

Potassium, sodium, and cancer: a review.

J Environ Pathol Toxicol Oncol, 15(2-4):65-73 1996

Agents known or believed to be carcinogenic decrease the concentration of potassium and increase the concentration of sodium in the cells. Anticarcinogenic agents have the opposite effect. In all cases where we have information on an agent's carcinogenicity or anticarcinogenicity and on that agent's effects on cellular potassium and sodium concentrations the above relationships have been found to be true. Dietary carcinogenic agents studied include sodium, cadmium, fat, cholesterol, calories, and alcohol; dietary anticarcinogenic agents include potassium, vitamins A, C, and D, selenium, and fiber. The effect of calcium intake is less clear as that effect depends on the concentrations on sodium and potassium. Not only dietary agents but also other carcinogenic and anticarcinogenic agents work in the same way. The cancer-causing drug dimethylhydrazine increases sodium and decreases potassium in the cells, whereas, for example, indomethacin, an anticarcinogen, has the opposite effect. In aging potassium leaves the cells, sodium enters them, and the rates of cancer increase. Patients with hyperkalemic diseases (Parkinson, Addison) have reduced cancer rates, and patients with hypokalemic diseases (alcoholism, obesity, stress) have increased cancer rates.

Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting.

J Thorac Cardiovasc Surg, 113(2):354-60; discussion 360-2 1997 Feb

OBJECTIVE: This prospective, randomized, clinical study was undertaken to determine whether glucose-insulin-potassium solutions would benefit patients undergoing coronary artery bypass grafting because of unstable angina. METHODS: The study group consisted of 30 patients with unstable angina who required coronary artery bypass grafting. In 15 patients, glucose-insulin-potassium solution (30% dextrose in water; K+, 80 mEq/L: regular insulin, 50 units) was given intravenously at 1 ml/kg per hour after induction of anesthesia and administration continued for 12 hours after aortic unclamping. Fifteen patients in a separate group received 5% dextrose in water intravenously at 50 ml/hr. RESULTS: Patients treated with glucose-insulin-potassium solution had higher cardiac indices (2.8 +/- 0.1 vs 2.0 +/- 1 L/min per square meter; p < 0.001), lower inotrope scores (0.06 +/- 0.01 vs 0.46 +/- 0.19; p = 0.041), and less weight gain (6.4 +/- 9 vs 11.6 +/- 1.1 pounds; p < 0.001) and had shorter times of ventilator support (8.3 +/- 0.6 vs 14.2 +/- 0.2 hours; p = 0.003). They had a significantly lower incidence of atrial fibrillation (13.3% vs 53.3%; p = 0.020) and had shorter stays in the intensive care unit (14.8 +/- 1.3 vs 31.6 +/- 5.2 hours; p = 0.002) and in the hospital (6.0 +/- 0.4 vs 8.0 +/- 0.7 days; p = 0.010). CONCLUSIONS: We conclude that glucose insulin-potassium therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting.

Effects of dietary sodium substitution with potassium and magnesium in hypertensive type II diabetics: a randomised blind controlled parallel study.

J Hum Hypertens, 10(8):517-21 1996 Aug

We have previously demonstrated that modest sodium restriction has a hypotensive effect in hypertensive diabetic subjects. A randomised blind controlled study has therefore been performed to study the effect of replacement of added salt intake using a salt substitute (50% NaCl, 40% KCL, 10% Mg2+, supplied by Cederroth, Sweden), compared to added whole salt intake over a 9 month period of 40 hypertensive Type II diabetic subjects (mean age 62.5 +/- 7.8 years; 24 males and 16 females). After 3 months, there was a significant reduction in systolic blood pressure (SBP) in the salt substitution group (163.2 +/- 24.2 to 153.6 +/- 20.8 mm Hg; P <0.03) which was maintained at 9 months, when compared to the whole salt group (151.5 +/- 20.6 vs 173 +/- 18.9 mm Hg; P ><0.05). No significant changes were observed in mean weight, fasting lipid or insulin levels or diabetic control (measured by glycosylated haemoglobin). A greater number of patients were withdrawn during the study period owing to consistent BP >160/95 in the whole salt group (n = 10) compared to salt substitute (n = 4). No significant changes were observed in diastolic pressure, 24-h urine sodium or magnesium excretion, but urine potassium was significantly increased in the salt substitute group (58.8 to 77.3: P < 0.05). The results of this study suggest that substitution of sodium, by potassium and magnesium, produces a clinically significant reduction in SBP in hypertensive Type II diabetic patients, and should be a useful antihypertensive therapy in this patient group.

Dietary calcium, potassium, magnesium and blood pressure in the Netherlands.

Int J Epidemiol, 10(6):1117-23 1995 Dec

BACKGROUND: The quantitative contribution of dietary calcium, potassium and magnesium to blood pressure levels remains unknown as does the combined effect of dietary calcium, potassium and magnesium. METHODS: The relation between blood pressure and dietary calcium, potassium and magnesium and the combined effect of these minerals on blood pressure was studied in 20,921 Dutch men and women aged 20-59 years. Food intake was measured by a food frequency questionnaire. The data were adjusted for age, body mass index, heart rate, alcohol and energy intake. RESULTS: An inverse association was observed between blood pressure and dietary potassium and magnesium in both men and women. Dietary calcium was inversely related to systolic blood pressure (SBP) in women and with diastolic blood pressure (DBP) in men. The relation between magnesium intake and blood pressure was stronger than those between blood pressure and intakes of potassium and calcium. Men and women who consumed a diet with intakes in the upper tertiles of all three minerals had a lower SBP and DBP compared to those who had intakes in the lower tertiles (men: SBP = -1.3 (95% CI: -2.6, -0.1), DBP = -1.9 (95% CI: -2.7, -1.0), women: SBP = -1.8 (95% CI: -3.1, -0.5), DBP = -1.5 (95% CI: -2.4, -0.7). CONCLUSION: These results suggest that diets rich in calcium, potassium and magnesium are associated with lower blood pressure.