Cited by 285Sodium Intake and HealthElectrolyte and hormonal disordersBlood Pressure and Hypertension Studies

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High dietary sodium chloride consumption may not induce body fluid retention in humans

Heer, Martina, Baisch, Friedhelm, Kropp, Joachim, Gerzer, Rupert, Drummer, Christian·2000·American Journal of Physiology-Renal Physiology

DOI 10.1152/ajprenal.2000.278.4.f585

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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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Method
Pathogenesis of Hypertension: Interactions Among Sodium, Potassium, and Aldosterone
Büssemaker, E., Hillebrand, U., Hausberg, M., Pavenstädt, H. J., & Oberleithner, H. (2010) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2009.12.022 · Cited by 72
Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients
Lindner, G., Schwarz, C. C., Kneidinger, N., Kramer, L., Oberbauer, R. W., & Druml, W. (2008) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfn476 · Cited by 72
“It is not possible to predict under which circumstances how much of the infused sodium will be stored in these pools [22–24].”
Background
Increasing sodium intake from a previous low or high intake affects water, electrolyte and acid–base balance differently
Heer, M., Frings-Meuthen, P., Titze, J., Boschmann, M., Frisch, S., Baecker, N., & Beck, L. (2009) · British Journal of Nutrition · doi:10.1017/s0007114508088041 · Cited by 69
“ECV was analysed by the sinistrin dilution method as described previously((3)).”
BackgroundMethodResultInfluential
High-Salt Diet Causes Osmotic Gradients and Hyperosmolality in Skin Without Affecting Interstitial Fluid and Lymph
Nikpey, E., Karlsen, T. V., Rakova, N., Titze, J. M., Tenstad, O., & Wiig, H. (2017) · Hypertension · doi:10.1161/hypertensionaha.116.08539 · Cited by 69
Do Bodybuilders Use Evidence-Based Nutrition Strategies to Manipulate Physique?
Mitchell, L., Hackett, D. A., Gifford, J. A., Estermann, F., & O'Connor, H. T. (2017) · Sports · doi:10.3390/sports5040076 · Cited by 69
“Similarly, the manipulations in sodium consumption will not change the volume of the intracellular or extracellular compartments, only modifying urinary sodium output [29].”
Beyond The Current Paradigm: Recent Advances in The Understanding of Sodium Handling – Guest Editors: Stanley Shaldon and Joerg Vienken: Water‐Free Sodium Accumulation
Titze, J. (2009) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2009.00569.x · Cited by 67
A Modern View of the Interstitial Space in Health and Disease
Stewart, R. H. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.609583 · Cited by 67
“In 2000, it was reported in a study of human subjects that a high salt diet induced an increase in plasma volume and total body sodium, but no increase in extracellular fluid volume or body weight and no increase in arterial blood pressure (38).”
Background
Dietary reference values for chloride
EFSA Panel on Nutrition, N. F. A. F. A. (., Turck, D., Castenmiller, J. J. M., Henauw, S. D., Hirsch‐Ernst, K. I., Kearney, J., Knutsen, H. K., Maciuk, A., Mangelsdorf, I., McArdle, H. J., et al. (2019) · EFSA Journal · doi:10.2903/j.efsa.2019.5779 · Cited by 68
“Renal excretion of chloride is coupled to that of sodium and potassium (Brungel et al., 2001; Gropper et al., 2009a; Heer et al., 2009; Birukov et al., 2016).”
BackgroundInfluential
Rubbing salt in the wound
Hatherill, M. (2004) · Archives of Disease in Childhood · doi:10.1136/adc.2003.045047 · Cited by 62
New insights into the pathophysiology of the dysnatremias: a quantitative analysis
Nguyen, M. K., & Kurtz, I. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00106.2004 · Cited by 62
“(19) demonstrated positive Na balance in healthy subjects on a metabolic ward without increases in body weight, expansion of the extracellular space, or [Na ]p.”
Background
Exercise-Associated Hyponatremia
Rosner, M. H. (2009) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2009.03.001 · Cited by 61
Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt
Soleimani, M., Barone, S., Luo, H., & Zahedi, K. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054294 · Cited by 73
The Significance of Duration and Amount of Sodium Reduction Intervention in Normotensive and Hypertensive Individuals: A Meta-Analysis
Graudal, N. A., Hubeck‐Graudal, T., Jűrgens, G., & McCarron, D. A. (2015) · Advances in Nutrition · doi:10.3945/an.114.007708 · Cited by 59
“In the 3 studies (31, 33, 34) in which the upper limit of the intervention was greater than the upper limit of usual TA B LE 1 C ha ra ct er is tic s of st ud ie s in cl ud ed in m ax im al ef fic ac y an al ys is 1”
Background
Extrarenal Na + Balance, Volume, and Blood Pressure Homeostasis in Intact and Ovariectomized Deoxycorticosterone-Acetate Salt Rats
Titze, J. M., Luft, F. C., Bauer, K. H., Dietsch, P., Lang, R., Veelken, R. A., Wagner, H., Eckardt, K., & Hilgers, K. F. (2006) · Hypertension · doi:10.1161/01.hyp.0000221039.17735.1a · Cited by 58
Antidiuretic Hormone and Serum Osmolarity Physiology and Related Outcomes: What Is Old, What Is New, and What Is Unknown?
Kanbay, M., Yılmaz, S., Di̇nçer, N., Ortíz, A., Sag, A. A., Covic, A. C., Sánchez‐Lozada, L. G., Lanaspa, M. A., Cherney, D. Z. I., Johnson, R. J., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01049 · Cited by 60
Quantification of nonosmotic sodium storage capacity following acute hypertonic saline infusion in healthy individuals
Engberink, R. O., Rorije, N. M. G., van den Born, B. H., & Vogt, L. (2017) · Kidney International · doi:10.1016/j.kint.2016.12.004 · Cited by 57
Water and sodium balance in space
Drummer, C., Norsk, P., & Heer, M. A. (2001) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2001.27765 · Cited by 57
High-Salt Diet Causes Expansion of the Lymphatic Network and Increased Lymph Flow in Skin and Muscle of Rats
Karlsen, T. V., Nikpey, E., Han, J., Reikvam, T., Rakova, N., Castorena‐Gonzalez, J. A., Davis, M. J., Titze, J. M., Tenstad, O., & Wiig, H. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311149 · Cited by 52
Exercise-Associated Hyponatraemia
Weschler, L. B. (2005) · Sports Medicine · doi:10.2165/00007256-200535100-00005 · Cited by 52
Vascular endothelial growth factor C levels are modulated by dietary salt intake in proteinuric chronic kidney disease patients and in healthy subjects
Slagman, M. C. J., Kwakernaak, A. J., Yazdani, S., Laverman, G. D., van den Born, J., Titze, J. M., & Navis, G. J. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr402 · Cited by 51
“Salt can be stored in a newly discovered subcutaneous interstitial compartment by binding to polyanionic proteoglycans and glycosaminoglycans without commensurate water retention [10, 11].”
Skin Sodium and Hypertension: a Paradigm Shift?
Selvarajah, V., Connolly, K., McEniery, C. M., & Wilkinson, I. B. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0892-9 · Cited by 55
Hyponatremia and Hypokalemia in Patients on Peritoneal Dialysis
Zanger, R. (2010) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2010.00789.x · Cited by 49
“New evidence from healthy subjects suggests that several grams of ingested Na may be retained in relative excess to water without changing the serumNa concentration (43).”
Background
Nutritional interventions related to bone turnover in European space missions and simulation models
Heer, M. A. (2002) · Nutrition · doi:10.1016/s0899-9007(02)00905-x · Cited by 49
Effects of dietary sodium chloride on health parameters in mature cats
Xu, H. Z., Laflamme, D. P., & Long, G. L. (2008) · Journal of Feline Medicine and Surgery · doi:10.1016/j.jfms.2008.10.001 · Cited by 48
Edelman's equation is valid in acute hyponatremia in a porcine model: plasma sodium concentration is determined by external balances of water and cations
Overgaard‐Steensen, C., Larsson, A., Bluhme, H., Tønnesen, E., Frøkiær, J., & Ring, T. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00412.2009 · Cited by 48
Central regulation of body fluid homeostasis
Noda, M., & Matsuda, T. (2022) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.98.016 · Cited by 48
Evolving concepts in the quantitative analysis of the determinants of the plasma water sodium concentration and the pathophysiology and treatment of the dysnatremias
Kurtz, I., & Nguyen, M. K. (2005) · Kidney International · doi:10.1111/j.1523-1755.2005.00652.x · Cited by 47
“These factors included (1) changes in the [Na+]pw due to intercompartmental H2O shifts in hyperglycemic states [7, 8]; (2) transcellular shifts of Na+ and K+ in hypokalemia-induced hyponatremia [15–17]; and (3) a component of the total Nae and Ke is osmotically inactive and incapable of modulating the [Na+]pw [9, 18–2…”
Background
Changes in Estimating Echocardiography Pulmonary Capillary Wedge Pressure After Hypersaline Plus Furosemide Versus Furosemide Alone in Decompensated Heart Failure
Parrinello, G., Paterna, S., Pasquale, P. D., Torres, D., Mezzero, M., Cardillo, M., Fasullo, S., Rocca, G. L., & Licata, G. (2010) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2010.11.003 · Cited by 46
A Quantitative Systems Physiology Model of Renal Function and Blood Pressure Regulation: Model Description
Hallow, K., & Gebremichael, Y. (2017) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12178 · Cited by 45
The "African gene" theory: it is time to stop teaching and promoting the slavery hypertension hypothesis.
Lujan, H., & DiCarlo, S. (2018) · Advances in Physiology Education · doi:10.1152/advan.00070.2018 · Cited by 11
“Despite retaining just as much salt as salt-sensitive subjects, saltresistant subjects do not develop hypertension (16, 17, 31, 32, 34, 36, 40, 46, 61, 65, 66, 68, 69, 79, 80).”
Background
Impact of Diuretic Treatment and Sodium Intake on Plasma Volume in Patients with Compensated Systolic Heart Failure
Bonfils, P. K., Damgaard, M., Taskiran, M., Goetze, J. P., Norsk, P., & Gadsbøll, N. (2010) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfq100 · Cited by 44
“The majority of ingested salt is excreted in the urine, with only a minor sodium loss through sweat and faeces.(18) In patients receiving chronic diuretic treatment, neutral sodium balance is achieved by increased sodium retention, and therefore, the average daily sodium excretion can be taken as an index for the diet…”
Background
Errors in Dual Energy X-Ray Absorptiometry Estimation of Body Composition Induced by Hypohydration
Rodríguez-Sánchez, N., & Galloway, S. D. R. (2014) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2014-0067 · Cited by 44
The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity?
Kurtz, T. W., DiCarlo, S. E., Pravenec, M., & Morris, R. C. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001458 · Cited by 42
Balancing wobbles in the body sodium
Titze, J. M., Rakova, N., Kopp, C., Dahlmann, A., Jantsch, J., & Luft, F. C. (2015) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfv343 · Cited by 43
20-Hz whole body vibration training fails to counteract the decrease in leg muscle volume caused by 14 days of 6° head down tilt bed rest
Zange, J., Mester, J., Heer, M., Kluge, G., & Liphardt, A. (2008) · European Journal of Applied Physiology · doi:10.1007/s00421-008-0899-z · Cited by 43
Are the total exchangeable sodium, total exchangeable potassium and total body water the only determinants of the plasma water sodium concentration?
Nguyen, M. K., & Kurtz, I. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfg112 · Cited by 41
“[20] demonstrated positive sodium balance in healthy subjects on a metabolic ward without increases in body weight, expansion of the extracellular space, or plasma sodium concentration.”
Background
Clinical impact of tissue sodium storage
Engberink, R. O., Selvarajah, V., & Vogt, L. (2019) · Pediatric Nephrology · doi:10.1007/s00467-019-04305-8 · Cited by 39
Dietary NaCl Does Not Affect Blood Pressure in Healthy Cats
Luckschander, N., Iben, C., Hosgood, G. L., Gabler, C., & Biourge, V. C. (2004) · Journal of Veterinary Internal Medicine · doi:10.1111/j.1939-1676.2004.tb02567.x · Cited by 39

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)
ORCID: Heer, Martina
Gerzer, Rupert
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
DOI: 10.1152/ajprenal.2000.278.4.f585
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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High dietary sodium chloride consumption may not induce body fluid retention in humans

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