Hydration and Disease
Friedrich Manz, MD
Research Institute of Child Nutrition, Dortmund, GERMANY
Key words: dehydration, hydration, hyperhydration, chronic diseases
Many diseases have multifactorial origins. There is increasing evidence that mild dehydration plays a role
in the development of various morbidities. In this review, effects of hydration status on acute and chronic
diseases are depicted (excluding the acute effects of mild dehydration on exercise performance, wellness,
cognitive function, and mental performance) and categorized according to four categories of evidence (I–IV).
Avoidance of a high fluid intake as a precautionary measure may be indicated in patients with cardiovascular
disorders, pronounced chronic renal failure (III), hypoalbuminemia, endocrinopathies, or in tumor patients with
cisplatin therapy (IIb) and menace of water intoxication.
Acute systemic mild hypohydration or dehydration may be a pathogenic factor in oligohydramnios (IIa),
prolonged labor (IIa), cystic fibrosis (III), hypertonic dehydration (III), and renal toxicity of xenobiotica (Ib).
Maintaining good hydration status has been shown to positively affect urolithiasis (Ib) and may be beneficial
in treating urinary tract infection (IIb), constipation (III), hypertension (III), venous thromboembolism (III), fatal
coronary heart disease (III), stroke (III), dental disease (IV), hyperosmolar hyperglycemic diabetic ketoacidosis
(IIb), gallstone disease (III), mitral valve prolapse (IIb), and glaucoma (III).
Local mild hypohydration or dehydration may play a critical role in the pathogenesis of several broncho-
pulmonary disorders like exercise asthma (IIb) or cystic fibrosis (Ib). In bladder and colon cancers, the evidence
on hydration status’ effects is inconsistent.
Key teaching points:
• Extremes of water intake, severe dehydration, and water intoxication, are known causes of mortality.
• It is now known that even mild dehydration may also account for different morbidity.
• Prolonged labor, urolithiasis, and urinary tract infection are examples of conditions associated with acute or chronic dehydration.
Many diseases have multifactorial origins. Particularly, dif-
ferences in lifestyle and environmental impact are implicated in
several diseases and constitute risk factors that are currently
being evaluated. The extremes of water metabolism, severe
dehydration, and water intoxication are well-known causes of
mortality. There is increasing evidence, however, that mild
dehydration may also account for different morbidity. This
review is a follow up to two earlier reviews [1,2] and is based
mainly on computer-based literature searches such as Medline.
The following markers of hydration status were used: [a] intake
(water OR fluid), [b] urine (volume OR osmolality), and [c]
hydration. Papers were classified according to the following
categories of evidence :
(Ia) evidence from meta-analysis of randomized controlled
(Ib) evidence from at least one randomized controlled trial;
(IIa) evidence from at least one controlled study without ran-
(IIb) evidence from at least one other type of quasi-experimen-
(III) evidence from descriptive studies such as comparative,
correlation, and case control studies; and
(IV) evidence from expert committee reports, opinions or clin-
ical experience of respected authorities, or both.
Address reprint requests to: Dr. Friedrich Manz, Research Institute of Child Nutrition, Heinstu ¨ck 11, D-44225 Dortmund, GERMANY. E-mail: email@example.com
Presented at the ILSI North America 2006 Conference on Hydration and Health Promotion, November 29–30, 2006 in Washington DC.
Conflict of Interest Disclosure: There are no conflicts of interest to declare in connection with this work.
Journal of the American College of Nutrition, Vol. 26, No. 5, 535S–541S (2007)
Published by the American College of Nutrition
Acute health effects of mild dehydration on exercise perfor-
mance, wellness, cognitive function, and mental performance
will be discussed by other authors in this supplement.
HYPERHYDRATION AND DISEASE
The short half-life time of water excretion of about 100 min
based on a high renal dilution capacity is an effective mecha-
nism to protect healthy subjects from hyperhydration .
Health Effects of Polydipsia and Polyuria
A high water intake may be pathogenic in certain diseases.
It is a routine clinical practice to recommend a moderately high
fluid intake in patients with cardiovascular disorders, low se-
rum albumin levels, or endocrinopathies (e. g. inappropriate
ADH secretion). Patients with chronic renal insufficiency were
urged to drink to be well-hydrated. However, a high fluid
intake with urine osmolalities below plasma osmolality may
accelerate the decline of glomerular filtration rate (category III
evidence) . Low urine osmolality is a determinant of cispla-
tin-induced nephrotoxicity in tumor patients, justifying the use
of concurrent intravenous infusion of osmotically active sub-
stances (category IIb evidence) .
Acute water intoxication with confusion, nausea, fatigue,
seizures, and even death has been considered a rare event
. In miners, steal workers, and firemen on a boat working
in the heat, uncompensated high sodium losses in sweat may
result in hyponatremia and non-osmolar vasopressin secre-
tion. An additional high intake of water with low sodium
content may decease hyponatremia further provoking con-
vulsions and even death. Water intoxication in infants may
result from repeated immersion during swimming  or
malicious forcing of water on a child , in toddlers from
near drowning or drowning , in marathon runners from an
uncontrolled high intake of fluids eventually combined with
the intake of anti-inflammatory drugs [10,11], in crash diet
potomania from a hypocaloric diet with a low renal osmolar
load and a slightly impaired maximum urine dilution ca-
pacity  and in psychotic patients from forced drinking
Iatrogenic water intoxication may be observed after rapid
infusion of high amounts of hypotonic solutions in infants with
hypertonic dehydration, during urine concentration test with
vasopressin analogues  or uncontrolled gastric lavage in
children after oral poisoning . Chronic hyperhydration may
result in chronic diarrhea .
MILD DEHYDRATIN OR
HYPOHYDRATION AND DISEASE
Mild hypohydration or dehydration may favor acute or
chronic, systemic, or local health effects.
Acute Systemic Mild Dehydration or
Oligohydramnios. Amniotic fluid is a complex substance
essential for fetal wellbeing. Both oligohydramnios and poly-
hydramnios are associated with a significant increase in peri-
natal morbidity and mortality. Simple and long-term maternal
hydration with oral water or intravenous hypotonic fluid ap-
peared to increase amniotic fluid volume and seemed to be
beneficial in the preventing and managing oligohydramnios
during labor (category IIa evidence) [17,18]. In pregnancy-
induced hypertensive gravidae, the effect on amniotic fluid
index was not as pronounced as in normotensive gravidae
(category IIa evidence) .
Prolonged Labor. Little is known about differences in
labor progress, birth outcomes, and neonatal status between
women who consume food and/or fluid during labor and
those who fast during labor . Increasing fluid adminis-
tration for nulliparous women in labor above rates com-
monly used was associated with a lower frequency of pro-
longed labor and possibly less need for oxytocin in a
randomized controlled study (category Ib evidence) .
Theoretically, hydration may reduce uterine contractility by
increasing uterine blood flow and by decreasing pituitary se-
cretion of antidiuretic hormone and oxytocin. In two small
studies, however, no advantage of hydration was observed
when compared to bed rest alone to stop preterm labor (cate-
gory IIa evidence) .
Cystic Fibrosis. Patients with cystic fibrosis show high
sodium content in sweat just below plasma sodium concentra-
tion. Sweat volume is mainly derived by contraction of extra-
cellular volume during physical activity and in the heat. As
losses of functional water are small, plasma osmolality rises
very little and there is almost no stimulus to drink . Patients
with cystic fibrosis, therefore, are especially prone to heat
injury. During the August 2003 heat wave in France, six out of
245 adult patients with cystic fibrosis developed extrarenal
dehydration with functional kidney failure, hypokalemia, and
hypochloremia. One patient died of malignant hyperthermia
(category III evidence) .
Hypertonic Dehydration in Infants. In infants, high pro-
tein and sodium content in formula and weaning food may
result in a submaximal urine osmolality, which increases the
life-threatening risk of hypertonic dehydration during acute
gastroenteritis (category III evidence) .
Hydration and Disease
536SVOL. 26, NO. 5
Dehydration and Toxicity of Xenobiotica. Contrast agents
used in angiography procedures are known to cause contrast-
induced nephropathy, especially in patients with mild dehydra-
tion. Prehydration is sufficient to prevent contrast-induced ne-
phropathy (category Ib evidence) .
CHRONIC SYSTEMIC MILD
There are many descriptive studies relating urolithiasis to
low fluid intake or urine volume. However, there is only one
randomized controlled study . The study consisted of 199
patients, who were divided into two groups. After the first
idiopathic stone episode, one group was instructed to increase
its fluid intake to achieve a urine volume of at least 2 L without
any further dietetic change, while the other group did not
receive any treatment. During the five year follow up periods,
patients from the intervention group had higher urine volume
(2.1–2.6 vs. 1.0– 1.2 1/24 h), a lower recurrence rate (12 vs.
27%), and a longer time to first recurrence (39 vs. 25 months)
(category Ib evidence). In Israel, primary prevention was dem-
onstrated comparing two desert towns with a high incidence of
urolithiasis. Inhabitants of one settlement participated in an
education program to increase fluid intake as a preventive
measure, whereas inhabitants of the second settlement were not
informed. Three years later, follow up on the intervention
population showed a higher urine output and a lower incidence
of urolithiasis (category IIb evidence) .
Two prospective studies with large cohorts confirm high
fluid intake’s preventive effect on symptomatic urolithiasis risk
(category IIb evidence) [29,30]. In a study on hot-area workers
presenting with low urine volumes had a nine-fold risk of
urolithiasis compared to room-temperature workers (category
IIb evidence) . Children with urolithiasis rarely comply
with high fluid intake recommendations despite their experi-
ence of pain during colic . Prolonged exposure to micro-
gravity during spaceflight increases the risk of renal stone
formation. Lower body negative pressure chamber treadmill,
alkali therapy, and aggressive hydration are recommended
countermeasures to decrease urinary supersaturation .
Urinary Tract Infection
Experimental and clinical data on the connection between
fluid intake and urinary tract infection risk are conflicting .
In two recent descriptive studies, poor fluid intake or low urine
output were host-mediated predisposing factors (category III
evidence) [35,36]. In two comparative studies, poor fluid intake
was much more frequent in females with urinary tract infection
than in controls (53% vs. 16%; 50% vs. 9.5%) (category III
evidence) [37,38]. Two years after implementing health edu-
cation and seasonal on-the-job training in 366 qualified female
workers, the number of water intakes and urine voids increased
and the prevalence of urinary tract infection decreased from
9.8% to 1.6% (category IIb evidence) .
Bladder and Colon Cancer
Two recent literature reviews and two meta-analyses inves-
tigating the relationship between total fluid intake and bladder
cancer show inconsistent findings (category III evidence) [40–
43]. Single studies point to increased bladder cancer risk in
patients that regularly consume high quantities of special bev-
erages or tap water (category III evidence) . Consuming
high quantities of contaminated water, such as tap water with a
high nitrate concentration, may increase colon cancer risk (cat-
egory III evidence) [45,46]. A high total fluid intake seems not
to account for an increased risk. Constipation and laxative use
may increase colon cancer risk (category III evidence). How-
ever, mild dehydration seems not to be a confounder .
A few studies have shown fluid restriction to increase
constipation . The beneficial effect of increased fluid intake
may perhaps be limited to subjects with dehydration . In a
retrospective, multi-center, case-control study, 73% of the chil-
dren with constipation drank less than four glasses of water per
day compared to 47% of those without constipation (category
III evidence) . In another study, 94 Japanese patients with
Parkinson’s disease had a much lower intake of coffee and tea
than controls (604 ml/d vs. 910 ml/d) . Constipation sever-
ity correlated inversely with the amount of water intake (cate-
gory III evidence) .
A potent renal vasopressin receptor agonist, dDAVP, mark-
edly reduced both urine flow and sodium excretion in healthy
humans . The impact of antinatriuresis by chronic high
vasopressin levels in mild dehydration on the pathophysiology
of hypertension, however, needs to be delineated. In diabetic
patients, lower urine flow and sodium excretion rates are as-
sociated with higher blood pressure during the day and a
reduced fall in blood pressure at night (category III evidence)
. The offspring of prenatally water-restricted ewes exhibit
hypernatremia and hypertension, indicating in utero program-
ming of an altered set point for systemic osmolality and blood
Hemoconcentration, polycythemia, and the special circum-
stances of travel-thrombosis are risk factors for thromboembo-
lism that are possibly intensified by dehydration. After an acute
ischemic stroke, venous thromboembolism was increased in
Hydration and Disease
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION537S
patients with serum osmolality values of more than 297
mosm/kg (category III evidence) . Long-distance travel
seems to be associated with increased venous thromboembo-
lism risk. Although the causal role of travel-related factors (e.g.
sitting in a cramped position, hypobaric hypoxia, low humidity
due to climatization, and reduced fluid intake) is not yet
proven, several scientific committees recommend maintaining
adequate hydration, exercising one’s legs, and using compres-
sion stockings (category IV evidence) . In vitro tests show
that changes in hydration can significantly impact adhesion,
causing normal erythrocytes to display adhesive properties
similar to those of sickle cells and vice versa .
Fatal Coronary Heart Disease
In the Adventist Health Study, a high water intake was
associated with a reduced risk of fatal cardiac heart disease
(category III evidence) . In Japanese taxi drivers, low water
intake at night might have caused increased blood coagulation,
hematocrit, and fatal cardiac heart disease risk .
Raised plasma osmolality or hematocrit on admission is
associated with increased risk of stroke morbidity and mortality
(category III evidence) [59,60]. In patients with ischemic
stroke, the best discharge outcome is associated with an initial
mid-range hematocrit level .
Although there is considerable circumstantial evidence to
indicate a link between dehydration and dental diseases, this
has not yet been proven . Hypohydration reduces salivary
excretion. Exercise dehydration may be the main reason for
loss of salivary protection of teeth. One aspect of individualized
patient-empowering erosion WATCH strategies to combat
tooth wear in healthy young Australians, therefore, is the rec-
ommendation for an adequate water intake during exercise
(category IV evidence) . Salivary protection of teeth may
be disturbed not only by quantity and composition of beverage
intake, but also by drinking habits. Infant bottle or breastfeed-
ing caries is an example that sipping from a bottle for too long
and breastfeeding too frequently favors dental caries .
Hyperosmolar Hyperglycemic Diabetic Ketoacidosis
In patients with diabetes mellitus, dehydration favored hy-
perglycemia development, whereas fasting resulted in reduced
plasma glucose concentrations (category IIb evidence) .
Elderly patients with diabetes mellitus are particularly vulner-
able to hyperglycemia and dehydration, the key components of
hyperosmolar hyperglycemic syndrome, because insulin sensi-
tivity and thirst mechanisms decrease with increased age .
In children with diabetic ketoacidosis, the serum osmolality
level on admission was the most important predictor of death
. In pediatric patients with newly diagnosed diabetes mel-
litus, high intakes of carbonated carbohydrate fluids favored a
more severe presentation of ketoacidosis .
Water ingestion has been shown to induce gallbladder emp-
tying and a high daily water intake could perhaps prevent
gallstone formation . In a case control study in a female
population, the main risk factors of gallstone disease were age,
family history of gallstone disease, fat intake, number of preg-
nancies, and menopause. Drinking water from a deep well was
a protective factor (category III evidence) .
Mitral Valve Prolapse
Mild dehydration induced echocardiographic-visible signs
of mitral valve prolapse in approximately 50% of healthy
asthenic women with previously normal cardiac findings. In
men, only 10% developed dehydration-induced mitral valve
prolapse (category IIb evidence) .
The difference between intraocular pressure and blood pres-
sure of ocular vessels plays a dominating role in the pathogen-
esis of glaucoma. The combination of a high intraocular pres-
sure and a low blood pressure is especially unfavorable. Oral
intake of water transiently increases intraocular pressure while
dehydration decreases it. In a retrospective analysis of the eyes
of 76 open-angle glaucoma patients, mean intraocular pressure
peak and percentage of intraocular pressure variation were
significantly higher during a water drinking test in patients with
visual field progression compared to patients without progres-
sion (category III evidence) . Eyes with higher glaucoma-
tous visual field damage presented with higher intraocular
peaks and fluctuations after water ingestion . In patients
with low-tension glaucoma and visual field defects, emotional
stress or cooling one hand in cold water may lead to ocular
vasospasms with low blood pressure and increased eye sensi-
tivity to intraocular pressure . In a case control study,
subjects with vasospastic syndrome reported a reduced desire
to drink, a lower estimated quantity of daily fluid intake, and
more episodes of low blood pressure (category III evidence)
LOCAL MILD HYPOHYDRATION OR
Improvement of systemic hydration status has not been
demonstrated to be clinically effective in disorders of the lungs
and airways . However, local water transport and hydration
status of mucus play a critical role in the pathogenesis of
Hydration and Disease
538S VOL. 26, NO. 5
several of these disorders. In exercise asthma, inhaling warm,
humidified air or medicaments that stabilize mucus hydration
status rapidly ameliorate the clinical picture (category IIb evi-
dence) . During exercise, the evaporative water loss from
the airway surface triggers mast cells to release inflammatory
mediators that stimulate bronchoconstriction . Persistent
inflammation leads to excessive production of mucus with high
viscoelasticity and adhesiveness. Inhaling hypertonic saline or
mannitol increased the clearance of mucus and improved the
quality of life in patients with mild asthma, bronchiectasis, and
cystic fibrosis . In patients with cystic fibrosis, the clinical
benefit of inhaled hypertonic saline was impeded by amiloride
inhibiting the osmotically-driven water transport (category Ib
evidence) . In 10 asthmatic patients and 10 controls, a
dry-air tachypnea challenge in the laboratory caused dehydra-
tion in the expired air in all subjects and bronchoconstriction in
half of the asthmatics but none of the controls (category IIb
evidence) . Humidifying the inspired air prevented bron-
choconstriction. In 19 healthy subjects, the net water loss in
expired air increased by 42% when the breathing mode was
switched from nasal to oral expiration . In a randomized
crossover study, aerosol administration of hyaluronic acid, a
substance with a unique capacity to link and to retain a partic-
ularly relevant number of water molecules, reduced the bron-
chial hyper-reactivity to exercise in asthmatics .
There are conditions where an individual may need to limit
fluid intake and they include cardiovascular disorders, end
stage chronic renal failure, hypoalbuminemia, and treatment
with cisplatin. Acute systemic mild hypo- or dehydration may
be a pathogenic factor in other conditions including oligohy-
dramnios, prolonged labor, patients with cystic fibrosis, hyper-
tonic dehydration in infants and renal toxicity of xenobiotics.
Chronic systemic mild- hypo- or dehydration also may be a
pathogenic factor in urolithiasis, urinary tract infection, consti-
pation, hypertension, venous thromboembolism, fatal coronary
heart disease, stroke, dental disease, hyperosmolar hyperglyce-
mic diabetic ketoacidosis, gallstone disease, mitral valve pro-
lapse and glaucoma. Local mild hypo-or dehydration may be a
pathogenic factor in bronchopulmonary disorders such as ex-
ercise asthma or cystic fibrosis.
Table 1 summarizes the conditions described herein and the
level of evidence supporting the associations. Few randomized
controlled trials exist. Most available evidence is from descrip-
tive studies, such as comparative studies, correlation studies,
and case control studies.
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Category of Evidence Classification
Category of Evidence
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