Water Physiology

Essentiality, Metabolism, and Health Implications

Stavros A. Kavouras, PhD

Costas A. Anastasiou, PhD

fluids but also for the digestion of other nutrients and as

Water is the most abundant molecule in the human body a defense from pathogens. In fact, there is equilibrium
that undergoes continuous recycling. Numerous functions between intestinal water secretion (through the
have been recognized for body water, including its function pancreatic juices, bile, gastric secretion, and saliva) and
water absorption that should be maintained within
as a solvent, as a means to remove metabolic heat, and as narrow limits, because disturbances in this equilibrium
a regulator of cell volume and overall function. Tight control result in diarrhea or constipation. Water movement
mechanisms have evolved for precise control of fluid across the intestinal epithelium may occur paracellularly
through the tight junctions and transcellularly through
balance, indicative of its biological importance. However,
cell membranes. Experiments in canine intestinal segments
water is frequently overlooked as a nutrient. This article have shown that the potential for water absorption
reviews the basic elements of water physiology in relation differs among the various parts of the intestine.
to health, placing emphasis on the assessment of water Specifically, the large intestine has a greater capacity to
absorb a hypotonic solution compared with the jejunum
requirements and fluid balance. Current recommendations are
or the ileum, whereas a negative net water flux is
also discussed. Nutr Today. 2010;45(6S):S27S32 observed in the duodenum in the presence of a hypotonic
solution.2 However, most of the water entering the
intestine is absorbed in the small intestine. From a total

L ife on earth has evolved as a consequence of the

presence of water. Although some alternative
theories have been suggested for the generation of life
in nonaqueous environments, virtually all known living
systems depend on water for survival. Water has many
of approximately 8 L, about 6.5 L is absorbed through
the small intestine, whereas the absorptive function of the
large intestine is limited to about 1.3 L.3 Although water
may diffuse to some extent through cellular membranes,
the hydrophobic properties of their lipid bilayer do not
properties that seem indispensable for the functioning of allow the degree of absorption required. Instead, the
cells.1 It is an excellent solvent for ions, required for nerve greater part of absorbed water is transferred through
signaling, enzyme activity, mineralization of organic channel systems, such as the aquaporins.4 Water
compounds, and the properties of DNA. It is also a master movement in the gastrointestinal tract is regulated by
of weak intermolecular interactions, such as hydrogen osmotic gradients and is linked to ionic movements.
bonds, necessary for the protein binding in their Specifically, absorption of water is linked primarily to the
substrates, and hydrophobic reactions, necessary for movement of sodium ions, whereas secretion is linked
protein structure. The high specific heat of water, in to the movement of chloride ions.5 This linkage to ionic
relation to other substances, makes it capable of absorbing movements is less essential to the large intestine,
or losing heat without a large temperature change, thus where absorption of even distilled water may occur.6
protecting living cells from massive temperature
changes that could cause cell impairment or even death.
Distribution of Water in Body Fluid Compartments
Metabolism The fluid compartments of the human body include
the intracellular fluid, accounting for 55% of total body
Absorption
water, and the extracellular fluid compartment. The
Water movement through the gastrointestinal wall has latter can be further subdivided into the intravascular
great significance, not only for the delivery of ingested fluid compartment or plasma (7.5% of total body water),

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Water Physiology

the rapidly equilibrating interstitial fluid and lymph attributed solely to differences in body composition,
(20%), and some smaller compartments (the slowly because it has been recognized that the hydration status
equilibrating interstitial fluid of dense connective tissue of fat-free body mass is not altered by age or sex.12
and cartilage, the inaccessible interstitial fluid in the These relatively high amounts of body fluids are
bones, and the transcellular fluid, which is produced by continuously recycled, with equilibrium being established
the secretory cells).7 Water distribution across the when fluid intake matches fluid loss. In fact, a water
capillary endothelium is controlled by the balance of deficit may occur over the course of a few hours when
filtration forces (that tend to move water from the plasma intake is reduced or losses are increased.
to the interstitial space) and reabsorption forces, as first
described by Starling.8 The main filtration forces are
Human Body Water Functions
the hydrostatic pressure that is caused by the pumping of
the heart and a less potent colloid osmotic pressure of Body fluids serve a variety of functions in the human
a negligible amount of protein that is trapped in the body, including a key role in the digestion, absorption
interstitial space. The major reabsorption pressure is the and transportation of other nutrients, formation and
plasma osmotic pressure that is attributed to the solute stability of cell structures, removal of waste products and
molecules in the plasma. toxins, as a solvent for biochemical reactions,
thermoregulation of the human body, and lubrication of
Integrated Regulation of Body Fluid Balance cavities such as joints. Cell physiologists also have
discovered new functions of cellular water. Because water
Water homeostasis is maintained by mechanisms that is the main constituent of the cells, cellular water and
sense changes in intravascular volume and plasma fluxes of water between extracellular and intracellular
osmolality.9 Changes in the intravascular volume are compartments are the primary factors affecting cell
sensed by peripheral volume and pressure receptors that volume, which in turn regulates a wide variety of cellular
induce the release of the antidiuretic hormone, arginine functions, such as epithelial transport, metabolism,
vasopressin, from the neurohypophysis. In addition, excitation, hormone release, migration, cell proliferation,
neuron-like cells, the osmoreceptors, located within the or even cell death.13
central nervous system, sense changes in plasma Given the numerous biological functions of water, as
osmolality and also trigger antidiuretic hormone release well as the fact that it is a main constituent of the
and the induction of thirst. A second important humoral human body, it is a surprising fact that water is often
factor in body fluid regulation is angiotensin II. This ignored as a nutrient. Most textbooks consider protein,
hormone may act directly, by stimulating the release of carbohydrate, and fat as the macronutrients because these
antidiuretic hormone in the central nervous system, nutrients provide energy. However, if we consider the
or indirectly, by stimulating aldosterone release, which quantities of water and the energy-producing nutrients
in turn induces sodium conservation, a subsequent needed for an average person, it becomes clear that water
increase in plasma osmolality, and expansion of the is the quintessential macronutrient. However, many
extracellular volume. Antidiuretic hormone is the key factor problems and considerations have arisen in the study
in renal water handling, promoting water reabsorption in of water in terms of human physiology and nutrition.
the nephron. Specifically, antidiuretic hormone binds
to its receptor in the basolateral membrane of the
Defining Water Requirements
principal collecting duct cells, initiating a cascade of
reactions that lead to the translocation of the aquaporin Defining the nutritional status of water as a nutrient,
2 water channels from intracellular vesicles to the apical usually referred to as fluid balance or hydration status
membrane, rendering this membrane permeable to water.10 and subsequently fluid needs, is a challenging task. The
main reason for this is that there is no reserve of water in
the human body, and thus, fluids must be continuously
Human Requirements and recycled. Ideally, fluid balance may be determined by
Recommendations measuring fluid gain (via nutrition and metabolic water
production) and fluid losses (via the urinary system, the
Human Body Water Content
respiratory tract, the skin, and the gastrointestinal system)
In healthy adult humans, total body water represents under controlled environmental conditions and over a
an average of 59% for males and 56% for females, set, relatively small amount of time. Such studies have
according to body mass. Large variation is observed yielded fluid needs in the range of 1.6 to 3.2 L, depending
across and within age groups, with infants having higher on the environmental conditions and the physical activity
values of water content.11 These variations may be performed by the subjects.14 More recently, isotope-labeled

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 Water Physiology

water has been used to measure body fluid turnover and whereas total fasting increased the negative water balance.
water needs by following the decline in hydrogen isotope These notions highlight the importance of water in
over time. This technique offers the advantage of measuring retaining internal homeostasis. In the case of salt
fluid balance under real conditions of daily living and has ingestion, retention of water would be necessary to
produced similar results to those of water balance studies.15 maintain plasma electrolytes in normal ranges, whereas in
Fluid dynamics may vary considerably within the the case of carbohydrate ingestion, their protein-sparing
same person over a period of a day, or even a few hours. effect decreased the need for removal of the nitrogen
Therefore, on many occasions, hydration status (ie, the products of protein break down, as occurred in the case
water status of the body at a specific time point) may of total fasting.
be of more interest than overall fluid balance. Many Another study of water deprivation with balanced energy
markers have been proposed for the assessment of intake for 3 to 4 days, published at the same time,
hydration status, including hematologic indices (such as described decreased efficiency and unhealthy appearance
plasma osmolality and sodium concentrations) and after dehydration, a slight change in voice, sunken and
urinary indices (ie, urine osmolality, urine color, and pale face, and cyanosed lips as characteristics of water
specific gravity); the assessment of total body water by deprivation that vanished a few hours after restoration of
bioelectrical impedance; and cardiovascular function fluid.21 This study reported that there was practically
measures (such as heart rate, blood pressure, and no increase in the plasma proteins or hematocrit,
orthostatic tolerance).16 These markers may provide a indicating that the volume of the blood was maintained
reasonable estimation of a deficiency (dehydration) or an at the expense of some other fluid compartment.
overload (overhydration) of fluid in the body; however. Dehydration led to an increased production of urea,
they cannot provide estimates of actual water needs. indicating that water deprivation is accompanied by
catabolism of body tissues, even if the energy needs
are met.
Water Deficiency
Although a clear picture of human physiology under
A general problem in the study of water as a nutrient chronic and severe dehydration has not been obtained,
is that there is a scarcity of studies examining the effect of the aforementioned studies indicate that chronic
long-term water deficiency and its complications in the dehydration represents a threat to body homeostasis and
human body. Acute mild dehydration (a 4% change health. Numerous later studies, mainly epidemiological
in body weight) provokes unfavorable effects in the in nature, have explored the association between
cardiovascular function as plasma volume drops. These hydration status and health. Although not consistent,
effects include an increase in stroke volume and a hydration status and fluid intake have been associated
concomitant increase in heart rate, to maintain constant with many chronic diseases, such as urolithiasis, urinary
cardiac output.17 In the periphery, dehydration decreases tract infections, bladder and colon cancer, constipation,
skin blood flow and sweating,18 thus compromising bronchopulmonary disorders, hypertension, cerebral
thermoregulation and increasing body core temperature.19 infarct, fatal coronary heart disease, venous
However, these levels of water deficiency are fixed rapidly thromboembolism, mitral valve prolapse, diabetic
by a decrease in body water loss and the stimulation of ketoacidosis, dental diseases, gallstones, glaucoma, and
thirst, 2 mechanisms that will be discussed later. dental diseases.22 This era of science provides
Long-term effects of water deprivation have not been continuous, promising research.
described in detail. The only experiments describing The period that is compatible with life, under
severe dehydration conditions were performed in 1944. conditions of full water deprivation, is not known. Some
In one of these experiments, involving a 6-day period of anecdotal cases of accidental incidents, such as the
water and/or food deprivation in healthy male soldiers, runner Mauro Prosperi, who lost his way in a sandstorm
it was found that body fluid loss follows a biphasic during the Marathon des Sables, have shown that water
manner: during the first 48 hours, the loss of fluid occurred deprivation may be sustained for more than 9 days, with
predominantly from the extracellular space and losses of body water as high as 13 kg. In critically ill,
subsequently from the intracellular space, with the net end-point patients, refusal to take rehydration and
effect being equal for both spaces at the end of the nutrition has been considered as a method of euthanasia
experiment.20 Lassitude was pronounced, and the that takes several days to a few weeks until death
authors reported that the subjects were irritable and occurs.23 This observation is certainly not applicable to
foolishly argumentative. Ingestion of a hypotonic healthy humans, because death may not be attributed
sodium solution when subjects were already dehydrated solely to dehydration; however, it may indicate that life
resulted in a reduction of water loss, and the same effect may be sustained for several weeks under full water
was observed when subjects ingested carbohydrates, deprivation in healthy humans.

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Water Physiology

Toxicity An interesting condition of water intoxication is

exertional hyponatremia, occurring in some athletes
Most nutrients display toxicity if their intake exceeds a during long ultraendurance events (93 hours). This type
critical threshold that represents the tolerable upper of water toxicity is associated with a fluid intake during
intake level. For water, no such threshold has ever been exercise that exceeds fluid losses via the sweat, without a
established, assuming that the functioning kidney concomitant replacement of sodium lost.28 Decreased
removes the excess fluid. However, in some circumstances, free water clearance from the kidney, because of
massive fluid intake may indeed provoke toxicity. In redistribution of cardiac output to the active muscle and
psychiatric patients, particularly those with schizophrenia, the skin capillary bed, as well as inappropriate secretion
polydipsia (excess intake of fluids) occurs frequently of antidiuretic hormone may contribute to this kind of
and may lead to dilutional hyponatremia, a condition also water toxicity.29 However, no adverse effects have
known as water intoxication. Although this kind of been reported as a result of chronically high intakes of
hyponatremia is usually associated with an inability to fluids, when intake approximates losses.
excrete water because of kidney and/or antidiuretic
hormone disturbances, some patients are reported to Recommendations
drink such a large fluid volume that they exceed the ability
of the kidney to excrete water.24 This kind of The first official and specific guideline for water intake was
hyponatremia leads to brain edema, causing neurological reported in 1964 by the Food and Nutrition Board of the
symptoms such as nausea, vomiting, delirium, ataxia, National Academies of Science of the United States.30 This
seizures, and coma, which in turn worsen the psychiatric report recommended that a reasonable standard for
symptoms of these patients.25 Water intoxication with calculating water allowance is 1 mL/kcal of food. In the
hyponatremia may appear also in many other clinical 1989 recommendations of the same body, it was stated
conditions accompanied by a primary defect in the renal that because of the low risk of water intoxication,
excretion of free water and a subsequent expansion of water requirements may increase to 1.5 mL/kcal, to cover
extracellular fluid, but these cases are not related to fluid variations in activity level, sweating, and solute load.
consumption.26 Based on the dietary intake data from A systematic approach to water requirements appeared
the third National Health and Nutrition Examination only recently, in the latest version of the Dietary
Survey (1988Y1994), the top 99th percentile of men aged Reference Intakes.14 These recommendations include
31 to 50 years was consuming 8.1 L of fluids per day, absolute values (in liters per day) as recommendations,
and 5% of that age group, more than 6.4 L/d. In a recent in terms of adequate intake across all age groups, total
study, 44 men aged 55 to 75 years increased their water water intake (a combination of drinking water,
intake by 2 L/d for 2 months, resulting in an improved beverages, and food), and water intake by drinking water
lower urinary tract function.27 In summary, because and beverages, assuming that food contributes to water
hyponatremia is extremely rare, no tolerable upper limit intake by approximately 19% (Table). Adequate intakes
has been set by the Institute of Medicine.14 for water vary from 0.7 L /d of total water in infants to

Table. Dietary Reference Intakes (Adequate Intakes) for Watera

Males Females
Age Group Total Water From Beverages From Food Total Water From Beverages From Food
0Y6 mo 0.7 0.7 0.0 0.7 0.7 0.0
7Y12 mo 0.8 0.6 0.2 0.8 0.6 0.2
1Y3 y 1.3 0.9 0.4 1.3 0.9 0.4
4Y8 y 1.7 1.2 0.5 1.7 1.2 0.5
9Y13 y 2.4 1.8 0.6 2.1 1.6 0.5
14Y18 y 3.3 2.6 0.7 2.3 1.8 0.5
19+ y 3.7 3.0 0.7 2.7 2.2 0.5
Pregnancyb 3.0 2.3 0.7
Lactationb 3.8 3.1 0.7
a
Values are expressed in liters per day.
b
In pregnancy and lactation, dietary reference intakes have been set in the age range of 14 to 50 years.
Data were obtained from the Institute of Medicine.14

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 Water Physiology

3.7 and 2.7 L /d in male and female adults, respectively. 3. Ma T, Verkman AS. Aquaporin water channels in
Special recommendations are provided for pregnancy and gastrointestinal physiology. J Physiol. 1999;517(pt 2):
breast-feeding. Recently, the European Food Safety 317Y326.
Authority prepared a report on water requirements 4. Matsuzaki T, Tajika Y, Ablimit A, Aoki T, Hagiwara H,
Takata K. Aquaporins in the digestive system. Med Electron
[EFSA Panel Dietetics Products, Nutrition (NDA); Microsc. 2004;37:71Y80.
Scientific Opinion on Dietary Reference Values for 5. Martinez-Augustin O, Romero-Calvo I, Suarez MD,
Water. EFSA J. 2010;8(3):1459; available online at Zarzuelo A, de Medina FS. Molecular bases of impaired
www.efsa.europa.eu]. As in the recommendations water and ion movements in inflammatory bowel diseases.
provided by the National Academies of Science of the Inflamm Bowel Dis. 2009;15:114Y127.
United States, the European committee provides 6. Nishinaka D, Kishino F, Matsuura A. Water and
adequate intakes for water in terms of absolute values for electrolyte absorption from hypotonic oral rehydration
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Interestingly, these values are considerably lower than 9. Boone M, Deen PM. Physiology and pathophysiology of
those proposed for the population of the United States. the vasopressin-regulated renal water reabsorption. Pflugers
Arch. 2008;456:1005Y1024.
10. Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK,
Conclusions Knepper MA. Vasopressin increases water permeability of
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Water is the most abundant and the most frequently aquaporin-CD water channels to plasma membrane. Proc Natl
recycled element in the human body. Its numerous Acad Sci USA. 1995;92:1013Y1017.
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significant nutrient in human nutrition. Future research 12. Visser M, Gallagher D, Deurenberg P, Wang J, Pierson RN Jr,
in water physiology should focus on the association Heymsfield SB. Density of fat-free body mass: relationship
between fluid balance or intake and disease, at with race, age, and level of body fatness. Am J Physiol.
both molecular and epidemiological levels, and the 1997;272:E781YE787.
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14. Institute of Medicine. Dietary Reference Intakes for Water,
Potassium, Sodium, Chloride and Sulfate. Washington, DC:
The National Academies, Food and Nutrition Board; 2004:
Stavros A. Kavouras, PhD, is assistant professor, Laboratory of Nutrition
73Y185.
& Clinical Dietetics, Department of Dietetics & Nutrition, Harokopio
15. Sawka MN, Cheuvront SN, Carter R 3rd. Human water
University, Athens, Greece.
needs. Nutr Rev. 2005;63:S30YS39.
Costas A. Anastasiou, PhD, is adjunct professor, Department of Food
16. Kavouras SA. Assessing hydration status. Curr Opin Clin
and Nurtrition Sciences, University of the Aegean, Myrina, Lemnos, Greece.
Nutr Metab Care. 2002;5:519Y524.
Drs Kavouras and Anastasiou have received a research grant and speaker
17. Gonzalez-Alonso J, Mora-Rodriguez R, Below PR, Coyle
honorarium from Danone Waters R&D. Dr Kavouras is also a Scientific
EF. Dehydration markedly impairs cardiovascular function
Consultant for the Gatorade Sports Science Institute.
in hyperthermic endurance athletes during exercise.
Correspondence: Stavros A. Kavouras, PhD, Department of Dietetics &
J Appl Physiol. 1997;82:1229Y1236.
Nutrition, Harokopio University, 70, El Venizelou Ave, 176 71 Athens, Greece
18. Nishiyasu TS, Shi XG, Mack GW, Nadel ER. Effect of
([email protected]).
hypovolemia on forearm vascular resistance control during
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19. Pitts GC, Johnson RE, Consolazio FC. Work in the heat
as affected by intake of water, salt and glucose. Am J
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