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Long-term health outcomes associated with hydration status

Nature Reviews Nephrology volume 20, pages 275–294 (2024)Cite this article

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Abstract

Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration — such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality — with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status.

Key points

  • A growing number of epidemiological studies have linked markers of underhydration, such as elevated plasma vasopressin, sodium at the upper end of the normal range, low urine volume and high urine osmolality, with an increased risk of adverse health outcomes such as the future development of chronic diseases and premature mortality.

  • Worldwide population surveys estimate that more than 50% of people drink less than recommended, indicating that consistent proper hydration may be beneficial for many individuals.

  • Chronic underhydration results in a new steady state of water balance with constantly activated water conservation mechanisms accompanied by an accumulation of organic osmolytes and persistent vasopressin secretion.

  • Adaptive changes to underhydration affect multiple physiological systems and may promote their deterioration.

  • Interventional trials with increased water intake are needed to prove causality and facilitate implementation of optimal fluid intake recommendations into general clinical practice.

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Fig. 1: Overview of the core response to a decrease in body water content.
Fig. 2: Integrative systemic responses to a decrease in body water content.
Fig. 3: Defining hydration status using markers of hydration.
Fig. 4: Principles of osmotic regulation and adaptation.
Fig. 5: Physiological and homeostatic processes that may underlie long-term health outcomes of chronic underhydration.

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Acknowledgements

N.I.D. and M.B. receive support from intramural program of NHLBI (NIH grants 1ZIAHL006077-10, 1ZIAHL006078-10, 1ZIAHL006079-10 to M.B.). S.E. was supported by grants from the Swedish Research Council (2022-01771), the Swedish Society for Medical Research (SG-22-0076), the Åke Wiberg Foundation (M21-0041), the Maggie Stephen Foundation (20202018), the Albert Påhlsson Foundation (211214SE), the Crafoord Foundation (20210603), the Swedish Society of Medicine (SLS-959724), the Swedish Heart and Lung Foundation (20200126), Skåne University Hospital and Region Skåne (2020-0358).

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Authors and Affiliations

  1. Laboratory of Cardiovascular Regenerative Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA

    Natalia I. Dmitrieva & Manfred Boehm

  2. Biology Department, Whitman College, Walla Walla, Washington, USA

    Paul H. Yancey

  3. Perinatal and Cardiovascular Epidemiology, Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden

    Sofia Enhörning

  4. Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden

    Sofia Enhörning

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N.I.D., P.H.Y. and S.E. researched data for the article, made substantial contributions to discussions of the content, wrote, reviewed and edited the manuscript before submission. M.B. made substantial contributions to discussions of the content, reviewed and edited the manuscript before submission.

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Correspondence to Natalia I. Dmitrieva.

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Competing interests

P.H.Y. has participated in research funded by Danisco A/S. S.E. has accepted conference fees from Danone Research and participates in research trials funded partly by Danone Research. N.I.D., M.B. declare no competing interests.

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Nature Reviews Nephrology thanks Daniel Bichet, Jens Titze and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Dmitrieva, N.I., Boehm, M., Yancey, P.H. et al. Long-term health outcomes associated with hydration status. Nat Rev Nephrol 20, 275–294 (2024). https://doi.org/10.1038/s41581-024-00817-1

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