BACKGROUND. The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions.
METHODS. Over the course of 2 separate space flight simulation studies of 105 and 205 days’ duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant. We studied the effect of salt-driven changes in mineralocorticoid and glucocorticoid urinary excretion on day-to-day osmolyte and water balance.
RESULTS. A 6-g/d increase in salt intake increased urine osmolyte excretion, but reduced free-water clearance, indicating endogenous free water accrual by urine concentration. The resulting endogenous water surplus reduced fluid intake at the 12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and weekly rhythmical mineralocorticoid release promoted free water reabsorption via the renal concentration mechanism. Mineralocorticoid-coupled increases in free water reabsorption were counterbalanced by rhythmical glucocorticoid release, with excretion of endogenous osmolyte and water surplus by relative urine dilution. A 6-g/d increase in salt intake decreased the level of rhythmical mineralocorticoid release and elevated rhythmical glucocorticoid release. The projected effect of salt-driven hormone rhythm modulation corresponded well with the measured decrease in water intake and an increase in urine volume with surplus osmolyte excretion.
CONCLUSION. Humans regulate osmolyte and water balance by rhythmical mineralocorticoid and glucocorticoid release, endogenous accrual of surplus body water, and precise surplus excretion.
FUNDING. Federal Ministry for Economics and Technology/DLR; the Interdisciplinary Centre for Clinical Research; the NIH; the American Heart Association (AHA); the Renal Research Institute; and the TOYOBO Biotechnology Foundation. Food products were donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda, and Unilever.
Natalia Rakova, Kento Kitada, Kathrin Lerchl, Anke Dahlmann, Anna Birukov, Steffen Daub, Christoph Kopp, Tetyana Pedchenko, Yahua Zhang, Luis Beck, Bernd Johannes, Adriana Marton, Dominik N. Müller, Manfred Rauh, Friedrich C. Luft, Jens Titze
(A) Time series of the sum of 24-hour urine Na+ (with accompanying anions), K+ (with accompanying anions), and urea osmolyte excretion (U2Na2KUreaV) and FWC in the representative subject 54 during the 205-day experiment. (B) Average FWC per salt intake phase in all 10 subjects (n = 1,644). (C) Quantification of the changes in FWC per salt intake phase or per 24-hour UNaV tertile. (D) Average urine osmolyte excretion (U2Na2KUreaV) per salt intake phase in the same 10 subjects (n = 1,646). (E) Quantification of the changes in urine osmolyte excretion per salt intake phase or per 24-hour UNaV tertile. (F–H) Relationship among 24-hour osmolyte excretion, designated 24-hour Na+ intake, designated 24-hour fluid intake, and 24-hour FWC in the urine. Data are expressed as the average ± SD (B and D) or as the Δ change ± SEM (C and E). Data were statistically analyzed by mixed linear model (C and E) or simple linear regression (F–H). Details on statistical analysis for Figure 2 are provided in the Supplemental Materials (page 64).