Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study

Abstract

Context Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear. Objective Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters. Design, setting, participants We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects. Results Potassium supplementation increased plasma phosphate (from 1.10 ± 0.19 to 1.15 ± 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 ± 0.21 to 1.01 ± 0.20 mmol/L, P < 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D3. Fractional calcium excretion decreased (from 1.25 ± 0.50 to 1.11 ± 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 ± 0.19 to 1.06 ± 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 ± 1.91 to 5.45 ± 2.51 mmol/24 hours, P < 0.001, and from 1.25 ± 0.50 to 1.44 ± 0.54 %, P = 0.004, respectively). Conclusions Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23. Clinical Trial Registration number NCT01575041

Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort

“…Yet, the association between urinary potassium excretion and FGF23 was independent of urinary phosphate excretion, as proxy for dietary phosphate intake [26]. Furthermore, current results were in line with a short-term placebo and diet-controlled intervention trial wherein potassium chloride supplementation led to a decrease of FGF23 levels in pre-hypertensive individuals [12]. Similar to the interventional study, participants with higher urinary potassium excretion had a lower fractional phosphate excretion, and a higher TMP/GFR, which are expected findings if FGF23 is directly decreased by potassium [27].…”

“…Similar to the interventional study, participants with higher urinary potassium excretion had a lower fractional phosphate excretion, and a higher TMP/GFR, which are expected findings if FGF23 is directly decreased by potassium [27]. In contrast, plasma phosphate concentrations did not differ between the urinary potassium excretion sex-specific tertiles, whereas in an intervention study, it was found that plasma phosphate increased after potassium supplementation [12]. This might indicate that the increase of plasma phosphate due to the lowering of FGF23 levels is a short-term effect.…”

“…In addition, randomized controlled trials found that potassium supplementation reduces blood pressure [8], probably at least in part through stimulation of natriuresis [9]. Interestingly, a number of animal and human studies have shown that higher potassium intake may influence plasma phosphate and fibroblast growth factor 23 (FGF23) levels [10][11][12]. Recently, it was demonstrated that potassium supplementation reduces plasma FGF23 levels in pre-hypertensive individuals [12].…”

“…Interestingly, a number of animal and human studies have shown that higher potassium intake may influence plasma phosphate and fibroblast growth factor 23 (FGF23) levels [10][11][12]. Recently, it was demonstrated that potassium supplementation reduces plasma FGF23 levels in pre-hypertensive individuals [12].…”

Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia

“…Rat studies have shown that a potassium deficiency can result in phosphaturia ( 38 ). Similarly, in humans, potassium supplementation leads to a decrease in FGF23 and an increase in serum phosphate levels ( 39 ). Hypokalaemia can occur in any patient with CS ( 40 ).…”