Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial.

Background: Low potassium has been identified both as a risk factor for type 2 diabetes and as a mediator of the racial disparity in diabetes risk. Low potassium could be a potentially modifiable risk factor, particularly for African Americans.Objective: We sought to determine the effects of potassium chloride (KCl) supplements, at a commonly prescribed dose, on measures of potassium and glucose metabolism.Design: Among African-American adults with prediabetes, we conducted a double-blinded pilot randomized controlled trial that compared the effects of 40 mEq K/d as KCl supplements with a matching placebo, taken for 3 mo, on measures of potassium and glucose metabolism, with measures collected from frequently sampled oral-glucose-tolerance tests (OGTTs).Results: Twenty-seven of 29 recruited participants completed the trial. Participants had high adherence to the study medication (92% by pill count). Participants in both groups gained weight, with an overall mean ± SD weight gain of 1.24 ± 2.03 kg. In comparison with participants who received placebo, urine potassium but not serum potassium increased significantly among participants randomly assigned to receive KCl (P = 0.005 and 0.258, respectively). At the end of the study, participants taking KCl had stable or improved fasting glucose, with a mean ± SD change in fasting glucose of -1.1 ± 8.4 mg/dL compared with an increase of 6.1 ± 7.6 mg/dL in those who received placebo (P = 0.03 for comparison between arms). There were no significant differences in glucose or insulin measures during the OGTT between the 2 groups, but there was a trend for improved insulin sensitivity in potassium-treated participants.Conclusions: In this pilot trial, KCl at a dose of 40 mEq/d did not increase serum potassium significantly. However, despite weight gain, KCl prevented worsening of fasting glucose. Further studies in larger sample sizes, as well as with interventions to increase serum potassium more than was achieved with our intervention, are indicated to definitively test this potentially safe and inexpensive approach to reducing diabetes risk. This trial was registered at clinicaltrials.gov as NCT02236598.

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension.

Angiotensin II (AngII) hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na(+) channel abundance and activating cleavage. Acutely raising plasma [K(+)] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K(+)] with a single 3-hour 2% potassium meal would lower NCCp in Sprague-Dawley rats after 14 days of AngII (400 ng/kg per minute). The potassium-rich meal neither decreased NCCp nor increased K(+) excretion. AngII-infused rats exhibited lower plasma [K(+)] versus controls (3.6±0.2 versus 4.5±0.1 mmol/L; P<0.05), suggesting that AngII-mediated epithelial Na(+) channel activation provokes K(+) depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K(+) depletion during AngII infusion and, thus, prevent NCC accumulation. A2K-fed rats exhibited normal plasma [K(+)] and 2-fold higher K(+) excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (P<0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. Epithelial Na(+) channel subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK (renal outer medulla K(+) channel abundance) abundance was unaffected by AngII or dietary K(+) In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by epithelial Na(+) channel stimulation.

Potassium Intake, Bioavailability, Hypertension, and Glucose Control.

Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+) ATPase pump. Approximately 90% of potassium consumed (60-100 mEq) is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect health outcomes. Hypertension (HTN) is the leading cause of cardiovascular disease (CVD) and a major financial burden ($50.6 billion) to the US public health system, and has a significant impact on all-cause morbidity and mortality worldwide. The relationship between increased potassium supplementation and a decrease in HTN is relatively well understood, but the effect of increased potassium intake from dietary sources on blood pressure overall is less clear. In addition, treatment options for hypertensive individuals (e.g., thiazide diuretics) may further compound chronic disease risk via impairments in potassium utilization and glucose control. Understanding potassium bioavailability from various sources may help to reveal how specific compounds and tissues influence potassium movement, and further the understanding of its role in health.

Comparison of potassium alone and potassium-magnesium supplementation in patients with heart failure using hydrochlorothiazide.

Supplementation of potassium alone and in combination with magnesium was compared in 10 patients with chronic compensated heart failure receiving hydrochlorothiazide 50 mg twice daily for the whole trial. After a 3-week run-in period, the patients were randomized to receive active supplementation for 6 weeks in a double-blind cross-over manner. A 3-week wash-out period was kept in between. Addition of 2 g potassium chloride daily (27 mmol K+) did not efficiently correct the serum potassium concentration. After the combined supplementation of 2 g potassium and 1 g magnesium (27 mmol K+ and 17 mmol Mg2+ daily), both serum potassium and magnesium concentrations increased statistically significantly during the first 2 weeks of treatment. After a longer treatment of 6 weeks, the effect of combined supplementation was less clear, even though a trend toward a better maintenance of serum potassium was still evident.

Inadequate supplies of potassium and magnesium in relief food--implications and countermeasures.

Analyses of relief food used in Ethiopia showed that, because of food refinement, 6 out of 10 samples of cereals contained too little potassium and magnesium to cover daily needs. Malnutrition is often associated with gastrointestinal infections, which lead to further deficiency of these electrolytes. Potassium and magnesium are required for protein synthesis, growth, and tissue repair. Since protein supplies are often marginal, relief food should contain sufficient potassium and magnesium to allow optimum utilisation of dietary nitrogen sources. This may be achieved by using coarse qualities of cereals, by supplementing cereals with legumes, and by avoiding cooking procedures that extract these salts from the cereals.

Current approaches to management of potassium deficiency.

Current issues related to oral potassium supplementation are reviewed, with emphasis on recommendations for the appropriate use of potassium supplementation for both replacement and preventive therapy. Dietary potassium intake, potassium-sparing diuretics, and the various forms of oral potassium supplements are reviewed in terms of indications for use, advantages, and limitations. Attention is given to controversial areas, i.e., gastrointestinal tolerance of controlled-release potassium oral dosage preparations and the need for potassium supplementation in hypertensive patients treated with diuretics.

Potassium supplements and total body potassium in elderly patients.

Total body potassium (TBK) and serum potassium measurements have been obtained in nine elderly patients in controlled heart failure on differing diuretic regimens. The patients were randomly maintained on a potassium-sparing diuretic, on frusemide, and on frusemide with potassium supplements (48 mmol/day) for a minimum of one month. TBK levels increased by a mean of 128 mmol on frusemide with potassium supplements compared with no supplements (P less than 0.001), a 7% increase in TBK. Serum potassium levels increased, similarly, from 4.1 mmol/l to 4.8 mmol/l (P less than 0.01). The potassium-sparing diuretic had the same effect as frusemide with supplements in increasing TBK in six patients. However, in three cases there was no increase in TBK compared with frusemide alone. The results demonstrate that potassium supplements are effective in raising TBK levels and serum potassium levels in elderly patients with heart failure.

Diuretics, potassium depletion and the risk of arrhythmias.

Evidence is available which suggests that the use of thiazide diuretics in the treatment of essential hypertension causes a fall in both plasma and total body potassium. The incidence of ventricular arrhythmias is proportional to the potassium deficit and may be enhanced by concomitant magnesium deficiency. Potassium loss may be minimized by limiting the dose of diuretic and by restricting sodium intake. Potassium chloride supplements are of relatively limited value and potassium-conserving diuretics are to be preferred in aviators. To reduce the potential risk of rhythm disturbance, aircrew receiving thiazide diuretics should be managed to ensure a serum potassium level at least 3.5 mmol l-1 after stabilization on therapy.

Potassium supplements or potassium-sparing agents.

During diuretic treatment alterations in myocardial cellular excitability due to potassium-induced disturbances of the membrane potential may arise without obvious changes of total body K. This may be explained by coexisting disturbances of the acid/base balance and other ions such as magnesium, two factors which independently influence the transport of potassium across the cell membrane. The consequence may be cardiac arrhythmias, particularly in the presence of digitalis. On the other hand hypokalemia, induced by diuretics, may also be accompanied by a significant depletion of total body K, bringing about more general consequences. It must be considered essential to maintain a normal general electrolyte balance during diuretic therapy. Potassium supplements may be used if true depletion of total body K is suspected, e.g. in hypokalemia with acidosis. Its use may, however, otherwise be questioned, as it is only directed towards the potassium situation and neglects the influence of diuretics upon other ions, such as H+ and Mg++. The potassium-sparing agents amiloride and triamterene normalize the general electrolyte situation in the distal tubules and should thus be regarded as drugs of first choice. Spironolactone has identical properties concerning the electrolytes but more serious side effects. It should be preferred when a significant secondary hyperaldosteronism is suspected and/or a more intense diuresis or an accentuated antihypertensive action is desired. The role of captopril in this context has not yet been established.

The role of potassium in the control of ammonium excretion during starvation.

Administration of KC1 0.5 mmol/kg/day to subjects undergoin prolonged starvation reduced daily urinary ammonium and beta-hydroxybutyrate excretion by one-third. These changes were accompanied by an improvement in potassium balance and an increased rate of chloride excretion. A similar fall in ammonium excretion occurred in a second group of subjects after administration of KHCO3 0.5 mmol/kg/day. Ketone body and bicarbonate excretion remained unchanged in this group while potassium balance improved. In both the first and second groups urine pH fell significantly as the rate of excretion of urinary buffer (ammonium) decreased. When the dose of KHCO3 was increased to 1.5-2.0 mmol/kg/day in fasting subjects, the urine was alkalinized, and ammonium excretion fell to negligible levels, resulting in nitrogen sparing of 2.0 g/day. The results indicate that one-half of the increase in ammonium excretion observed in starvation is due to potassium deficiency. Nitrogen wastage caused by losses of urinary ammonium during starvation can be virtually eliminated by potassium supplementation and urinary alkalinization. The decrease in beta-hydroxybutyrate excretion after potassium chloride administration was not caused by a fall in the rate of nonionic diffusion of this organic acid related to the reduction in urine pH. The reason for the fall in beta-hydroxybutyrate excretion is not apparent, though it was associated with an increase in chloride excretion.

Total body potassium in long-term frusemide therapy: is potassium supplementation necessary?

Measurements of total body potassium (T.B.K.) were made by whole-body counting in four groups of patients receiving oral frusemide for one year. Patients in group 1 had essential hypertension and normal renal function and received 40 mg frusemide daily without potassium supplements. Patients in group 2 were similar but received oral potassium supplements for the first four months of treatment. Patients in group 3 had hypertension associated with renal disease and received 120 mg frusemide daily without potassium supplements. Patients in group 4 also had hypertension and renal impairment and in addition to 120 mg frusemide daily they received oral potassium supplements for four months. No evidence of depletion of T.B.K. was found in any of the groups after continuous treatment with frusemide for one year. It is questioned whether potassium supplementation in long term diuretic therapy with frusemide is necessary unless there is evidence of pre-existing potassium depletion or of some other factor such as cardiac failure, cirrhosis of the liver, or the nephrotic syndrome.