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High dietary sodium chloride consumption may not induce body fluid retention in humans
Abstract
A commonly accepted hypothesis is that a chronically high-sodium diet expands extracellular volume and finally reaches a steady state where sodium intake and output are balanced whereas extracellular volume is expanded. However, in a recent study where the main purpose was to investigate the role of natriuretic peptides under day-to-day sodium intake conditions (Heer M, Drummer C, Baisch F, and Gerzer R. Pflügers Arch 425: 390-394, 1993), our laboratory observed increases in plasma volume without any rise in extracellular volume. To scrutinize these results that were observed as a side effect, we performed a controlled, randomized study including 32 healthy male test subjects in a metabolic ward. The NaCl intake ranged from a low level of 50 meq NaCl/day to 200, 400, and 550 meq/day, respectively. Plasma volume dose dependently increased (P < 0.01), being elevated by 315 +/- 37 ml in the 550-meq-NaCl-intake group. However, in contrast to the increased plasma volume, comparable to study I, total body water did not increase. In parallel, body mass also did not increase. Mean corpuscular volume of erythrocytes, as an index for intracellular volume, was also unchanged. We conclude from the results of these two independently conducted studies that under the chosen study conditions, in contrast to present opinions, high sodium intake does not induce total body water storage but induces a relative fluid shift from the interstitial into the intravascular space.
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“The gains of this controller must be chosen to reproduce the ultimate effect of this mechanism: maintenance of CNa at equilibrium levels (±1 mmol/L) after a perturbation such as an increase in Na intake.42, 43”
From A Quantitative Systems Physiology Model of Renal Function and Blood Pressure Regulation: Model Description (2017) · cites this paper as [43]
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“Furthermore, kinetics of Na homeostasis and the response to changes in Na intake vary considerably among species (8, 16, 17, 25, 33, 41).”
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Goswami, N., Roessler, A., Lackner, H. K., Schneditz, D., Grasser, E. K., & Hinghofer-Szalkay, H. G. (2009) · Clinical Autonomic Research · doi:10.1007/s10286-009-0001-x · Cited by 29
“We, however, did not attempt to monitor sodium balance as sodium balance is a controversial issue which goes beyond classical concepts [34]; inter-compartmental sodium shifts occur from and to the interstitial (‘‘third’’) compartment which potentially invalidate the significance of day to day sodium input (dietary ana…”
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Comparison of 24-Hour Whole Body versus Patch Tests for Estimating Body Surface Electrolyte Losses
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Huhn, K., Linz, P. R., Pemsel, F., Michalke, B., Seyferth, S., Kopp, C., Chaudri, M. A., Rothhammer, V., Dörfler, A., Uder, M., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102549118 · Cited by 24
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Thowsen, I., Reikvam, T., Skogstrand, T., Samuelsson, A., Müller, D. N., Tenstad, O., Alitalo, K. K., Karlsen, T. V., & Wiig, H. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.19777 · Cited by 27
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“ment-time interaction on urine volume [F(1,16) 6.”
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Florian, J. P., Baisch, F. J., Heer, M. A., & Pawelczyk, J. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118812 · Cited by 21
“Recent terrestrial [30] and spaceflight [28,31] studies suggest that instead of altered renal function and sodium handling, the hypocaloric nutrition and activation of alternative energy resources may have altered the water binding capacity and thus the distribution and cumulative balance of total body water.”
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Tangram of Sodium and Fluid Balance
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“20 Experimental salt loading of humans and rats led to a puzzling excess of sodium compared with water, 13–17 which reminds of Tangram paradoxes (E shapes): 2 figures composed with the same 7 pieces, one of which incomprehensibly seems to be a subset of the other (solution shown in Figure S3).”
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Urine sodium composition in ambulatory healthy children: hypotonic or isotonic?
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“This has been shown to be true in adults, as sodium loading did not cause appreciable change in serum sodium [5, 6].”
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“Long-term balance studies on humans have confirmed that considerable amounts of Na + accumulate in the interstitium due to excessive NaCl consumption (12-14).”
Matsushita, N., Kitazato, K. T., Tada, Y., Sumiyoshi, M., Shimada, K., Yagi, K., Kanematsu, Y., Satomi, J., & Nagahiro, S. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.198762 · Cited by 17
“Discussion Studies on the long-term balance of Na in humans ingesting a high-salt diet suggested its storage in water-free form.(14) Kopp et al,(15) who performed (23)Na magnetic resonance imaging studies of tissue sodium recently demonstrated Na storage in patients with hyperaldosteronism.”
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“In humans, the effect of an abrupt increase in sodium intake for 5–28 days on BP is also related to age; in younger subjects ( 26 yr of age), BP and plasma [Na ] do not rise (25, 32).”
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Skin-specific mechanisms of body fluid regulation in hypertension
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“Heer et al suggested that skin sodium losses could be neglected during long-term experiments, but the conclusions were based on three subjects constrained in a metabolic ward for 48 h [52].”
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Mutchler, A. P., Haynes, A. P., Saleem, M., Jamison, S., Khan, M. M., Ertuğlu, L. A., & Kirabo, A. (2025) · Circulation Research · doi:10.1161/circresaha.124.325439 · Cited by 14
Toward quantification of loop diuretic responsiveness for congestive heart failure
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“rounding interstitial fluid so that the interstitium acts a body Na buffer capable of storing excess Na.(23,24) In this way, the interstitial and intravascular Na concentrations and osmotic pressures remain relatively”
BackgroundInfluentialArcand, J., Wong, M., Trieu, K., Leung, A. A. C., Campbell, N. R. C., Webster, J. L., Johnson, C., Thout, S. R., McLean, R. M., & Neal, B. C. (2015) · Journal of Clinical Hypertension · doi:10.1111/jch.12762 · Cited by 14
“Table S4 contains errors in sodium intake and BP values for Burnier and colleagues(17) and Heer and colleagues.(18) A detailed analysis of all the extracted data has not yet been conducted.”
BackgroundDoes Excess Tissue Sodium Storage Regulate Blood Pressure?
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The Contribution of Skin Glycosaminoglycans to the Regulation of Sodium Homeostasis in Rats
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“A number of previous studies (Heer et al. 2000, Palacios et al. 2004, Titze et al. 2002a.) reported on the short term changes in volume of body fluid compartments following Na + ingestion : increment in total body mass as well as body fluid content were observed.”
BackgroundSchierbauer, J., Günther, S., Haupt, S., Zimmer, R. T., Zunner, B., Zimmermann, P., Wachsmuth, N., Eckstein, M., Aberer, F., Sourij, H., et al. (2022) · Italian National Conference on Sensors · doi:10.3390/s22093104 · Cited by 11
“However, since even small changes in osmolarity can be expected to have a marked effect on water transfer [17,18], it is possible that sensor performance might also be impaired by these changes, although the absolute fluid intake in this study was rather small [19].”
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“Salt loading accompanied by short-term increase in water intake was found in healthy volunteers,[28,30,37] but not during chronic adaptation to increased salt consumption.”
BackgroundMechanisms of sodium‐mediated injury in cardiovascular disease: old play, new scripts
Rossitto, G., & Delles, C. (2021) · FEBS Journal · doi:10.1111/febs.16155 · Cited by 12
Peltonen, L. M., & Sankari, S. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048769 · Cited by 12
“Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin.”
A new formula for predicting alterations in plasma sodium concentration in peritoneal dialysis
Nguyen, M. K., & Kurtz, I. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00387.2004 · Cited by 12
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“The researchers proved that an increase in salt intake does not cause water storage in the body, but only its displacement [68].”
Larina, I. M., Kolchanov, N. A., Доброхотов, И. В., Иванисенко, В. А., Сергеевич, Д. П., Tiys, E., Valeeva, O. A., Pastushkova, L. K., & Николаев, Е. Н. (2012) · Human Physiology · doi:10.1134/s0362119712030061 · Cited by 11
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Spaceflight Metabolism and Nutritional Support
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Salt intake and body fluid volumes: Have we learned all there is to know?
Humphreys, M. H. (2001) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(01)80027-5 · Cited by 11
Fluid balance and kidney function in space
Santo, N. G. D., Christensen, N. J., Drummer, C., Kramer, H. J., Regnard, J., Heer, M. A., Círillo, M., & Norsk, P. (2001) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2001.27751 · Cited by 11
Tissue sodium content in hypertension and related organ damage
Kolwelter, J., Uder, M., & Schmieder, R. E. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002580 · Cited by 10
“Opposing for the first time the current clinician’s thinking, an accumulation of Na without simultaneously commensurate water and rather a shift of water from the interstitial to the intravascular space were documented [3].”
BackgroundThe role of intra- and interdialytic sodium balance and restriction in dialysis therapies
Lew, S. Q., Aşçı, G., Rootjes, P. A., Ok, E., Penne, E. L., Sam, R., Tzamaloukas, A. H., Ing, T. S., & Raimann, J. G. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1268319 · Cited by 17
Estimation of sodium and chloride storage in critically ill patients: a balance study
Hessels, L., Lansink‐Hartgring, A. O., Zeillemaker‐Hoekstra, M., & Nijsten, M. W. (2018) · Annals of Intensive Care · doi:10.1186/s13613-018-0442-2 · Cited by 11
Is the osmotically inactive sodium storage pool fixed or variable?
Nguyen, M. K., & Kurtz, I. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00614.2006 · Cited by 10
“(6) demonstrated positive Na balance in healthy subjects on a metabolic ward without increases in body weight, expansion of the extracellular space, or plasma Na concentration ([Na ]).”
BackgroundNutritional Countermeasures for Spaceflight-Related Stress
Heer, M. A., Baecker, N., Smith, S. M., & Swart, S. R. (2011) · Springer eBooks · doi:10.1007/978-3-642-22272-6_29 · Cited by 10
Dialysis Unphysiology and Sodium Balance
Kim, G. (2009) · Electrolytes & Blood Pressure · doi:10.5049/ebp.2009.7.2.31 · Cited by 9
The New Heart Failure Diet: Less Salt Restriction, More Micronutrients
Rothberg, M. B., & Sivalingam, S. K. (2010) · Journal of General Internal Medicine · doi:10.1007/s11606-010-1254-8 · Cited by 9
The Human Penchant for Deranged Salt Balance
Leshem, M. (2013) · Frontiers in neuroscience · doi:10.1201/b15544-2 · Cited by 8
Fluid and Electrolyte Metabolism
Heer, M. A., Titze, J. M., Smith, S. M., & Baecker, N. (2015) · SpringerBriefs in space life sciences · doi:10.1007/978-3-319-18521-7_4 · Cited by 8
Sodium Fate after Sodium Bicarbonate Infusion: Influence of Altered Acid-Base Status
Adrogué, H. J., Awan, A. A., & Madias, N. E. (2020) · American Journal of Nephrology · doi:10.1159/000506274 · Cited by 8
Skin sodium content as a predictor of blood pressure response to renal denervation
Günes-Altan, M., Schmid, A., Kannenkeril, D., Linz, P. R., Ott, C., Bosch, A., Schiffer, M., Uder, M., & Schmieder, R. E. (2023) · Hypertension Research · doi:10.1038/s41440-023-01450-4 · Cited by 8
Evidence Report: Risk Factor of Inadequate Nutrition
Smith, S. M., Zwart, S. R., & Heer, M. A. (2015) · NASA STI Repository (National Aeronautics and Space Administration) · Cited by 8
Energy and fluid metabolism in microgravity
Heer, M. A., Elia, M., & Ritz, P. (2001) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200107000-00011 · Cited by 8
Sodium intake in Germany estimated from sodium excretion measured in spot urine samples
Klenow, S., Thamm, M., & Mensink, G. (2016) · BMC Nutrition · doi:10.1186/s40795-016-0075-5 · Cited by 7
“However, sodium intake equals urinary excretion at a sodium intake level that is supposed to be normal (~200 mmol/d) [63].”
BackgroundInfluentialSumiyoshi, M., Kitazato, K. T., Yagi, K., Miyamoto, T., Kurashiki, Y., Matsushita, N., Kinouchi, T., Kuwayama, K., Satomi, J., & Nagahiro, S. (2015) · Brain Research · doi:10.1016/j.brainres.2015.04.051 · Cited by 8
“4D).”
Pathophysiologie der Hypertonie
Jordan, J. (2015) · Der Internist · doi:10.1007/s00108-014-3572-0 · Cited by 8
Sodium intake does not influence bioimpedance-derived extracellular volume loss in head-down rest.
Hinghofer-Szalkay, H. G., László, Z., Passath, H., Pilz, K., Rössler, A., Ježová, D., & Scharfetter, H. (2004) · PubMed · Cited by 8
Leshem, M. (2014) · Appetite · doi:10.1016/j.appet.2014.11.014 · Cited by 8
Accessory Renal Arteries—Mostly, But Not Always, Innocuous
Kem, D. C., Lyons, D. F., Wenzl, J. E., Halverstadt, D. B., & Xiao, Y. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005101131 · Cited by 8
Interactions Among Artificial Gravity, The Affected Physiological Systems, and Nutrition
Heer, M. A., Baecker, N., Zwart, S. R., & Smith, S. M. (2007) · Springer eBooks · doi:10.1007/0-387-70714-x_9 · Cited by 7
“In some metabolic balance studies we demonstrated that on Earth high NaCl intake also leads to sodium retention without fluid retention (Heer et al. 2000a) and may induce mild metabolic acidosis (Frings et al. 2005).”
SKIN LYMPHATIC SYSTEM IN THE PATHOGENESIS OF ARTERIAL HYPERTENSION – REVIEW AND CRITIQUE
Chachaj, A., & Szuba, A. (2021) · Lymphology · doi:10.2458/lymph.4662 · Cited by 7
Masenga, S. K., Pilić, L., Hamooya, B. M., Nzala, S. H., Heimburger, D. C., Mutale, W., Koethe, J. R., Kirabo, A., Munsaka, S. M., & Elijovich, F. (2022) · Clinical Hypertension · doi:10.1186/s40885-022-00209-2 · Cited by 7
“However, decades ago, this sequence of events was disputed by investigators who found body weight and volume losses during increased salt intake [19].”
BackgroundSalt is getting under our skin
Rabelink, T. J., & Rotmans, J. I. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp399 · Cited by 7
Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat
Beauséjour, A., Houde, V., Bibeau, K., Gaudet, R., St‐Louis, J., & Brochu, M. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00090.2007 · Cited by 7
“For decades, the relationship between sodium intake and extracellular fluid volume, arterial pressure, and the renin-angiotensin system has been investigated extensively (22, 29).”
BackgroundOsmotically Inactivated Sodium in Acute Hyponatremia: Stay With Edelman
Adrogué, H. J., & Madias, N. E. (2019) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2019.04.021 · Cited by 7
Metadata
- Authors
- Heer, M., Baisch, F., Kropp, J., Gerzer, R., & Drummer, C.
- Affiliations
- Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) (DE)
- Technische Universität Dresden (DE)
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2000-04-01
- Volume
- 278
- Issue
- 4
- Pages
- F585-F595
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2140024548
- Cited by
- 285
- References
- 25
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 19 · 2018: 16 · 2017: 21 · 2016: 6 · 2015: 17 · 2014: 11 · 2013: 5 · 2012: 7
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Nephrology › Electrolyte and hormonal disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- high sodium intake, dietary salt, plasma expansion, extracellular volume, total body water, fluid retention, fluid shifts, interstitial fluid, mean corpuscular volume, natriuretic peptides, sodium balance
- MeSH terms
- Adult, Blood Pressure, Blood Volume, Body Fluid Compartments, Body Fluids, Body Water, Body Weight, Diet, Sodium-Restricted, Diuresis, Electrolytes, Hormones, Humans, Male
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