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

Jelmer K Humalda, Stanley M H Yeung, Johanna M Geleijnse, Lieke Gijsbers, Ineke J Riphagen, Ewout J Hoorn, Joris I Rotmans, Liffert Vogt, Gerjan Navis, Stephan J L Bakker, Martin H de Borst, Jelmer K Humalda, Stanley M H Yeung, Johanna M Geleijnse, Lieke Gijsbers, Ineke J Riphagen, Ewout J Hoorn, Joris I Rotmans, Liffert Vogt, Gerjan Navis, Stephan J L Bakker, Martin H de Borst

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.

Keywords: Diet controlled clinical trial; calcium-phosphate metabolism; fibroblast growth factor 23; nutrition; potassium; sodium.

© Endocrine Society 2020.

Figures

Figure 1.
Figure 1.
Effect of a 4-week period of potassium supplementation in (A) healthy prehypertensive adults on plasma phosphate (P = 0.004), (B) 24 hours urinary phosphate excretion (P = NS), and (C) TmP/GFR (P < 0.001). The rise of phosphate levels was paralleled by (D) a decrease in FGF23 (P = 0.01), (E) without effect on PTH (P = NS) or (F) 25[OH]-vitamin D3 (P = NS). Depicted are unadjusted means and standard error, or geometric means and 95% confidence intervals for FGF23 and PTH. Abbreviations: FGF23, fibroblast growth factor 23; NS, not significant; TmP/GFR, tubular maximum reabsorption of phosphate per glomerular filtration rate.
Figure 2.
Figure 2.
Spearman’s rho correlation coefficients for changes in blood and urine parameters in response to potassium (grey shaded area, lower left-hand side) or sodium (white area, upper right-hand side) supplementation vs placebo. ***P < 0.001, **P < 0.01, *P < 0.05. Abbreviations: Ca2+, calcium; eGFR, estimated glomerular filtration rate; FEP, fractional phosphate excretion; FGF23, fibroblast growth factor 23; K+, potassium; Na+, sodium; P, phosphate; TmP/GFR, tubular maximum reabsorption of phosphate per glomerular filtration rate; vit. D, 25(OH)-vitamin D3.
Figure 3.
Figure 3.
Effect of a 4-week period of sodium supplementation in healthy prehypertensive adults (A) on plasma phosphate (P = 0.03), 24 hours urinary phosphate excretion (B) (P = NS) (C) and TmP/GFR (P = NS). The rise of phosphate levels was paralleled by (D) a decrease in FGF23 (P = 0.02), (E) without effect on PTH (P = NS) or (F) 25[OH]-vitamin D3 (P = NS). Depicted are unadjusted means and standard error, or geometric means and 95% confidence intervals for FGF23 and PTH. Abbreviations: FGF23, fibroblast growth factor 23; TmP/GFR, tubular maximum reabsorption of phosphate per glomerular filtration rate.

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