Supplement Article
Determinants of water and sodium intake and output
Anna E. Stanhewicz and W. Larry Kenney
Physiological regulation of sodium and water intake and output is required for the
maintenance of homeostasis. The behavioral and neuroendocrine mechanisms that
govern fluid and salt balance are highly interdependent, with acute and chronic
alterations in renal output tightly balanced by appropriate changes in thirst and, to
a lesser extent in humans, sodium appetite. In healthy individuals, these tightly coupled mechanisms maintain extracellular fluid volume and body tonicity within a
narrow homeostatic range by initiating ingestive behaviors and the release of
hormones necessary to conserve water and sodium within the body. In this review,
the factors that determine output of sodium and fluid and those that determine
“normal” input (i.e., matched to output) are addressed. For output, individual variability accompanied by dysregulation of homeostatic mechanisms may contribute
to acute and/or chronic disease. To illustrate that point, the specific condition of
salt-sensitive hypertension is discussed. For input, physical characteristics, physiological phenotypes, genetic and developmental influences, and cultural and environmental factors combine to result in a wide range of individual variability that, in
humans, is compensated for by alterations in excretion.
INTRODUCTION
In humans, water and sodium balance are tightly regulated by physiological control systems that act mainly
through neuroendocrine mechanisms. These finely tuned
physiological mechanisms adjust thirst and, to a lesser
extent, mechanisms that affect sodium intake, as well as
renal excretion of fluid and sodium to maintain fluid
homeostasis. Stimulated primarily by changes in the volume or electrolyte content of the extracellular fluid, these
control systems regulate appropriate compensatory
mechanisms to bring sodium balance back to within a
narrowly defined range. Despite a great deal of individual
variability in sodium and water intake, these systems are
remarkably precise and work in concert. Changes in output are balanced by changes in intake and vice versa to
achieve sodium balance for maintenance of extracellular
fluid volume and free water balance for maintenance
of body tonicity in the steady state. However, in some
cases, idiopathic and/or pathological alterations in
physiological control result in the abnormal regulation of
sodium and water balance.
A full treatise on thirst, salt appetite, and renal
function is beyond the scope of this review. Instead, this
brief review provides an overview of the physiological
regulation of sodium and water balance. Specifically,
those factors that determine the intake of sodium and
fluid and those that determine “normal” output (i.e.,
matched to intake), as well as the populations and conditions in which dysregulation occurs are addressed.
First, the focus is on the output side of the equation; the
conditions under which individual variability accompanied by dysregulation of the sensitive regulatory mechanisms may contribute to acute and/or chronic disease
are considered. In that regard, the specific condition of
salt-sensitive hypertension is discussed. On the input
side, physical characteristics, physiological phenotypes,
genetic and developmental influences, and cultural and
environmental factors combine to result in a wide range
of individual variability.
Affiliation: A.E. Stanhewicz and W.L. Kenney are with the Noll Laboratory, Department of Kinesiology, The Pennsylvania State University,
University Park, Pennsylvania, USA. Correspondence: W.L. Kenney, Department of Kinesiology, The Pennsylvania State University, University
Park, 102 Noll Laboratory, PA, 16802-6900, USA. E-mail: [email protected]. Phone: +1-814-863-1672.
Key words: hydration, salt intake, sodium balance, thirst, water balance.
C The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For
V
Permissions, please e-mail: [email protected].
doi: 10.1093/nutrit/nuv033
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OUTPUT: WATER CLEARANCE AND
SODIUM EXCRETION
Despite the large variability in daily water and sodium
intake, extracellular volume is maintained within a narrow range in healthy humans. The kidneys are the primary organs responsible for the control of fluid and
electrolyte balance as they can handle large variations in
salt and water load with great efficiency. Daily, the kidneys can excrete 0.5–25 L of urine with osmolality that
varies from 40 to 1400 mOsm/kg H2O. Thus, depending
on the physiological demands, urine volume and osmolality can vary 50-fold and 35-fold, respectively.1 This
tight control is accomplished primarily through alterations in sodium and water reabsorption via mechanisms
stimulated by the volume and tonicity of the plasma.
Renal water clearance
Total body water is tightly regulated by sensitive and
precise mechanisms that are activated by deficits or surfeits of water amounting to only a few hundred milliliters. The increased tonicity of the plasma and decreased
plasma volume associated with dehydration triggers a
release of the antidiuretic hormone vasopressin from
the posterior pituitary. Vasopressin then increases water
reabsorption in the kidney, resulting in a more highly
concentrated urine and lower urine volume.1 When
there is an excess of water, the reverse occurs: low tonicity inhibits vasopressin release and the kidney excretes
water, resulting in production of more dilute urine.
Collectively, renal sodium reabsorption (discussed below) is a primary determinant of renal water retention.
However, the ability to concentrate or dilute the urine
is a critical physiological mechanism for the prevention
of dehydration or, conversely, water intoxication.
The ability to appropriately concentrate and dilute
urine decreases with age. Baseline urine osmolality ranges
from 40 to 1400 mOsm/kg in healthy young adults.2,3
However, older adults have a decreased range, with a minimal value of 92 mOsm/kg and an upper limit between 500
and 700 mOsm/kg for most adults aged >70 years.2,4
Under typical conditions, a healthy young adult with a
urine volume of 1.5–2 L/day clears approximately 900–
1200 mOsm/day. Under conditions that necessitate extreme water conservation and in the presence of high concentrations of vasopressin, this obligatory volume can
decrease to 0.75–1 L/day. During maximum aquaresis, it
can require up to 20 L/day to remove the same solute load.3
Diabetes insipidus (DI), a disease in which either
vasopressin secretion (central or neurogenic DI) or its
effects on the kidney (nephrogenic DI) are reduced, results in an exaggerated free water diuresis due to the inability to reabsorb free water. However, because
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sodium-conserving mechanisms are unaffected, there is
no accompanying sodium deficiency. Consequently, although untreated DI can lead to hypertonicity and mild
plasma volume depletion, until water depletion becomes severe, volume is preserved by osmotic shifts of
water to the more concentrated extracellular fluid, at a
cost to intracellular fluid.5 In the case of aging and
pathological disorders that limit the range of urine
osmolality, the inability to concentrate or dilute urine
sufficiently may lead to water imbalance in instances of
unusually high or low water intake.6 However, alterations in sodium reabsorption and resultant shifts in
the osmotic pressure of the extracellular fluid provide
protection under most conditions.
Renal sodium excretion
Sodium handling in the kidney starts with filtration by
the glomeruli, followed by reabsorption along the
proximal tubule and loop of Henle, with final adjustments made in the collecting tubules. Since sodium
represents <1% of the extracellular fluid by weight, the
mass of sodium required for maintenance of isotonic
extracellular fluid volume is quite small relative to the
volume of water that must be consumed. Accordingly,
the most critical aspect of sodium regulation in response to fluid loss and the resultant decrease in extracellular fluid volume is sodium retention by the
kidney. This retention is mediated, in part, by release
of the steroid hormone aldosterone from the adrenal
cortex, which increases the number and activity of epithelial sodium channel (ENaC) along the collecting
duct, increasing sodium reabsorption in the kidney.
Along with glomerulotubular balance and tubuloglomerular feedback, elevated aldosterone concentrations
can stimulate near-total sodium conservation, a regulatory mechanism that is essential for survival.
In addition, renin released from the juxtaglomerular apparatus in response to decreasing blood volume
increases circulating angiotensin II, which is a powerful
stimulus for thirst, acts to increase sodium reabsorption, and stimulates further release of aldosterone.
Conversely, when extracellular fluid volume expands,
blood pressure rises and the concomitant rise in perfusion pressure of the kidney causes an increase in sodium excretion. The increase in excretion is enhanced
by the release of atrial natriuretic peptide from the atrial
myocytes, which increases the filtered load of sodium
and counteracts sodium-conserving pathways. In
healthy individuals, variability in sodium ingestion is
balanced by tight physiological control of sodium excretion. However, alterations in these control mechanisms
may contribute to pathologies originally attributed to
ingestion, such as salt-sensitive hypertension.
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Figure 1 Illustration of the nonlinear relationship between salt intake and cardiovascular risk. Almost half of the US population is hypertensive or salt sensitive. However, only about half of the people who are hypertensive are also salt sensitive. Consequently, a low-salt diet
may not benefit everyone and may, in fact, paradoxically increase blood pressure in some individuals. Because of this variability, it is unclear
for whom low-salt diets are most beneficial. Adapted from Felder et al.7
Salt-sensitive hypertension
The pathogenic mechanisms associated with salt-sensitive hypertension have not been clearly elucidated.
Almost half of the US population is hypertensive, saltsensitive, or both.7 Salt sensitivity, defined as a transient
rise in blood pressure associated with acute salt ingestion, affects approximately 25% of the population.
However, only about half of those salt-sensitive people
are hypertensive. Consequently, the relationship between salt intake and cardiovascular risk is not linear
but rather fits a j-shaped curve, such that a low-salt diet
may not benefit everyone and may, in fact, paradoxically increase blood pressure in some individuals
(Figure 1).7 Because of this variability in both salt sensitivity and hypertension, it is unclear for whom low-salt
diets are most beneficial, making it likely that recent
widespread recommendations for extremely low sodium (<1500 mg/day) consumption are overly
conservative.
There is some evidence to support the hypothesis
that salt-sensitive hypertension is under genetic control,
as demonstrated by studies showing that salt-sensitive
individuals tend to have family histories of salt-sensitive
hypertension.8,9 Furthermore, salt sensitivity is more
prevalent in people of African origin.10 Interestingly, a
study on renal transplant patients found that recipients
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of kidneys from donors with a negative family history
of hypertension had lower blood pressure than those
who received kidneys from donors with a family history
of hypertension.11 Similarly, genetic variants in vascular
endothelial cells, nephron number,12 the sympathetic
nervous system, and the dopaminergic system have all
been implicated in the genetic predisposition to salt
sensitivity and salt-sensitive hypertension (Table 1).13
One hypothesis that has been proposed to describe
the mechanistic pathology of salt-sensitive hypertension is
a larger renal reabsorption of sodium. Polymorphisms of
the genes that regulate the renin–angiotensin–aldosterone
system,14 as well as renal ion transporters,15,16 have been
suggested to contribute to the genetic inability to regulate
sodium excretion in response to excess sodium ingestion.
It is likely that genetic variability in the renal handling of
sodium contributes to high blood pressure in salt-sensitive individuals.
INTAKE: THIRST AND DETERMINANTS OF SALT
INTAKE
Thirst
Total fluid intake over a daily period is regulated by
both homeostatic control mechanisms that respond to
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Table 1 Genetic variants implicated in salt sensitivity
System
Renin-angiotensin
Aldosterone and mineralocorticoids
Sympathetic nervous system
Renal sodium transport
Vascular endothelium and
smooth muscle
Genetic variant identified
Angiotensin-converting enzyme
Angiotensinogen
Angiotensin type 1 receptor
Aldosterone synthase
Serum/glucocorticoid regulated
Kinase 1
11-b-hydroxysteroid dehydrogenase
Cytochrome P450 3A
Tyrosine hydroxylase
B-adrenergic receptor diplotype
46AA/79CC
Adducin
Renal chloride channels
Adrenomedullin
Dopamine, dopamine receptors,
and GRK4
Endothelial nitric oxide synthase
Eicosanoids
Endothelin
Proposed mechanism
Increased renal sodium transport and/or vascular
smooth muscle–cell reactivity
Increased renal sodium reabsorption
Increased sympathetic activity and/or response
Increased renal sodium transport and reabsorption
Attenuated endothelium-dependent vasodilation
and/or increased vasoconstriction response
Figure 2 Mechanisms that drive daily fluid ingestion. Total fluid intake over a daily period is regulated by homeostatic control mechanisms
that respond to physiological need and nonhomeostatic behaviors. Abbreviations: ADH, antidiuretic hormone; ang II, angiotensin II; AVP, arginine vasopressin; BP, blood pressure; ECF, extracellular fluid.
physiological need and nonhomeostatic behaviors that
are heavily influenced by psychological and environmental stimuli (Figure 2). The latter include factors such as
beverage taste, appeal, and availability, as well as the coincident timing of fluid intake with meals. The physiological manifestations of thirst are characterized as a
combination of sensations that increase with dehydration
and decrease with rehydration. Thirst is characterized by
a dry, scratchy mouth and throat; chapped and dry lips;
and, in extreme cases, may be accompanied by lightheadedness, dizziness, tiredness, irritability, and headache.
Physiological thirst is stimulated by the following 2 distinct homeostatic mechanisms: increases in plasma tonicity (primarily dictated by plasma sodium concentration)
and reductions in extracellular fluid volume.
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An elevation in plasma tonicity, dictated by total
exchangeable sodium, total exchangeable potassium,
and total body water,17 is the most potent stimulus of
thirst, with only a 2%–3% change in plasma osmolality
required to induce thirst in humans.18 Osmoreceptors
located in the central nervous system control arginine
vasopressin release from the hypothalamus and posterior pituitary.19 In humans, plasma osmolality is highly
correlated with both thirst sensations and plasma arginine vasopressin concentrations.18,20,21
Hypovolemic thirst mechanisms are less sensitive
than are hypertonic mechanisms and are only initiated
when extracellular fluid volume falls by approximately
10%. Nerve endings that are responsible for detecting
changes in plasma volume, the so-called low-pressure
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baroreceptors, are located in the superior and inferior
vena cava and the atria of the heart. These baroreceptors detect alterations in stretch of vessel walls and the
myocardium that occur in response to changes in
venous pressure and central blood volume, respectively.
Studies aimed at examining the role of central lowpressure receptors in the drive to drink have used headout water immersion to preserve cardiac filling pressure
or limit its fall in the face of decreasing plasma volume.22,23 In hypovolemic young men and women, these
studies suggest that central volume expansion attenuates thirst, even in the presence of dehydration and increased plasma tonicity.23,24
Collectively, changes in plasma tonicity and central
blood volume initiate a global response that includes
adjustments in both thirst and sodium ingestion.
Redundancy in these mechanisms decreases the likelihood of error in these feedback loops.
Interindividual variation in fluid intake (and output)
On average, humans ingest approximately 2.2 L of fluid
per day, with approximately 80% of that volume from
pure water and beverage consumption and the remaining approximately 20% as constituent fluid in food.
Additionally, there is approximately 0.3 L of water produced as a byproduct of metabolism, resulting in an
average of 2.5 L of fluid gained daily. In order to maintain fluid balance, this intake must be met by fluid
losses; on average, approximately 1.5 L of urine output,
approximately 0.1 L of fecal water loss, and insensible
water losses of approximately 0.9 L through the skin (including sweat) and lungs result in daily fluid balance.
There is a great deal of individual variability in these
values due to differences in body size and adiposity,
pathological needs during illness and disease, and cultural influences and daily habits that effect fluid intake.
Furthermore, variation in insensible losses, specifically
sweat output accompanying physical activity and thermal stress, contribute a great deal to individual variation in fluid output and subsequent intake. Factors such
as age, heat acclimation, and physical fitness all affect
sweat losses and are reviewed more extensively elsewhere in this special issue.25
Total body water varies inversely with body fat content and directly with lean body mass. Consequently,
adult women have a lower percent of their total body
weight comprised of water compared with adult men because they have, on average, a greater percent body fat.
Obesity further reduces (and leanness increases) water
as a percentage of total body mass at any age and across
both sexes. Body water content and its distribution (intracellular vs extracellular) undergoes changes from early
fetal life through childhood and into early adulthood,
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such that approximately 79% of total body weight is water at birth compared with 58% by the age of 16 years.26
This relative loss of total body water mass is primarily
due to a decrease in extracellular water (from 44% at
birth to 19% by early adulthood).27 Consequently, infants have a higher relative extracellular fluid volume
and, thus, have more sodium per kilogram of fat-free
mass than adults.26 These variables may influence daily
fluid requirements26 and alter the thirst stimulus associated with a given fixed volume of fluid loss.
Taken together, cultural and environmental factors
lead to wide variations in fluid intake, output, and hydration status across populations, while personal habits and
variation in physiological needs dictate large differences
among individuals. For example, for healthy adults taking part in the INTERSALT study, large differences in
mean 24-hour urine volume and mean urine osmolality
from 52 centers throughout the world suggest large intercultural differences in hydration.28 Also from the
INTERSALT study, age- and sex-adjusted estimates of
intraindividual reliability for urine volume indicate a
lower intraindividual variance in 24-hour urine volume
than between-individual variance.29 Similarly, in a study
of individual plasma sodium concentration, Zhang
et al.30 found that serial plasma sodium values for any
given individual tended to cluster around a patientspecific set point and that these set-points varied widely
among individuals. In the Dortmund Nutritional and
Anthropometric Longitudinally Designed (DONALD)
study, which examined 3024 validated 24-hour urine
samples from 630 children and adolescents, urine osmolality was 742 6 218 mOsm/kg (mean 6 standard deviation) and interindividual variance explained 34% of total
variance.28 Collectively, these data suggest that, on an individual basis, it is easy to examine and characterize
acute hydration status (hyperhydration, euhydration, or
hypohydration) based on osmolar urine outputs or
plasma sodium concentration. However, when group
means and population studies are examined, it may be
more appropriate to classify hydration status based on
physiological measures such as urine osmolality as a “relative risk” of hyperhydration or hypohydration due to
large between-subject variability in healthy individuals.28
It is well established that the drive to drink is
closely associated with the level of dehydration.31 In experimental manipulations of osmotic thirst, hypertonic
saline infusion induces a powerful and linear thirst
response.18,20 Similarly, hypohydration preceding lowintensity exercise magnifies the drive to drink such that
participants ingest more fluid and, consequently, fully
restore hormonal and circulatory measures of hydration.32 Despite multiple reports that older adults drink
less than younger adults following dehydration,33–36
studies of apparently healthy, independently living older
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Figure 3 Age does not influence ad libitum fluid intake, output, or balance in healthy adults. Average fluid intake, output,
and net fluid balance in young men (YM), older men (OM), young
women (YM), and older women (OM) in a controlled water-balance
study of healthy individuals. Chronological age does not influence
ad libitum intake, output, or fluid balance in healthy adults.
Adapted from Bossingham et al.39
adults suggest that age, per se, does not influence ad libitum water intake,37 control of fluid balance, or indices
of hydration38,39 (Figure 3). Older individuals may ingest less fluid compared with young adults; however,
this is likely explained by age-associated changes in lean
body mass, physical activity, and sweating that decrease
daily fluid requirements in this population. Collectively,
these studies suggest that despite the variability in
individual requirements, the mechanisms associated
with thirst and maintenance of fluid balance are tightly
controlled in healthy individuals and are preserved
throughout older adulthood.
Sodium intake
Sodium appetite, i.e., the drive to behaviorally ingest
salt, is a specific neural response stimulated by sodium
deficiency. Sodium appetite is well characterized in animals that actively seek out pure salt, have special sense
organs to detect it, and will seek and ingest the sodium
ion in high concentrations following periods of deficiency. Humans, however, do not fit the biological
model for exhibiting a true sodium appetite. Humans
reject pure salt, prefer to eat salt in foods, reject the taste
of high concentrations of sodium in solution, and will
only ingest the chloride form of salt, whereas animals
will ingest almost any sodium anion. More importantly,
acute sodium deficit does not arouse salt hunger in
adult humans.40 It should be noted that 1 g of table salt
contains 0.4 g of sodium, and consumption of 2.5 g of
table salt provides 1 g of sodium. A complete discussion
of the effects of the accompanying anion on physiological responses to sodium ingestion is outside the scope
78
of this review; however, it may be relevant for acid–base
balance and in populations that are sensitive to sodium
intake.
Human sodium consumption has evolved with the
human diet. Hunters and gatherers consumed very low
amounts of sodium, a practice that persisted until approximately 5000 years ago and may explain the evolution of the kidney to conserve nearly all sodium filtered
at the glomerulus. During the period of history in which
salt was primarily used as a food preservative, very high
dietary sodium intakes were noted. Subsequently, the
advent of cold storage led to a decline in sodium consumption that persisted until the recent rise of processed foods, which drives today’s extremely high
sodium consumption in industrialized societies.
Total body water depends on the amount of sodium present in the extracellular space and the appropriate volume of water required to achieve isotonicity.
As such, sodium ingestion is required for proper hydration and fluid balance. It should be noted that when
salty foods or fluids are freely available, humans spontaneously exhibit a baseline level of sodium intake in excess of any immediate need. This elevated baseline salt
ingestion is adequate for maintaining fluid balance under normal conditions, i.e., in the absence of significant
sodium or fluid loss.
Unlike thirst, increased salt “appetite” is not stimulated by a decrease in the plasma concentration of
sodium (hyponatremia). In fact, dietary sodium deprivation results in neither hyponatremia nor a stimulus
for enhanced sodium ingestion,41,42 although hypernatremia may inhibit salt intake.43,44 The physiological
signals that drive sodium intake are not completely understood, with evidence supporting potential roles for
aldosterone, angiotensin II, baroreceptor input, and sodium content of the cerebral spinal fluid.45 Production
of the mineralocorticoid aldosterone is tightly coupled
to sodium deprivation,46,47 and the ingestive behavior
stimulated by aldosterone is uniquely specific to sodium, with little effect on fluid consumption.48,49
Angiotensin II, an important stimulus for thirst during
hypovolemia, may also increase sodium intake. Animal
studies suggest that angiotensin II infusion directly into
the brain stimulates a rapid increase in both water and
saline intake.50 However, intravenous administration of
angiotensin II rapidly increases water intake, with no
effect on appetite for saline.51 Additionally, a boost in
circulating angiotensin II following sodium depletion
neither accelerates the onset of sodium appetite nor increases the volume of saline ingestion,52 so the role of
angiotensin II in sodium appetite remains controversial.
Intracerebral sodium content is directly related to that
of the blood plasma, and increased sodium concentration in this compartment stimulates thirst and decreases
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sodium appetite. However, whether a reduction in intracerebral sodium increases sodium appetite remains
unclear.
Whether baroreceptor signaling is relevant for the
stimulation of sodium appetite likewise remains unclear.
Salt ingestion after prolonged hypovolemia is greatly reduced if the right atrium is distended with a balloon cannula, then rebounds after the cannula is deflated.53
Similarly, sodium appetite is reduced in rats after transection of the nerves that transmit sensory information
from arterial baroreceptors, suggesting a role for atrial
baroreceptors in modulation of sodium appetite in that
species.54 In summary, the physiological signals that determine sodium intake in humans remain generally
undefined. These signals provide feedback to centralized
receptors in the forebrain that regulate the motivation to
ingest salt in response to deficits in plasma sodium
content.45
Free-living adults typically ingest sodium well in
excess of physiological need. The daily required sodium
intake is debatable and is affected by a number of variable factors such as environmental conditions, physical
activity, and the physiological regulation of sodium balance. However, the worldwide average salt intake per
individual is approximately 10 g/day, which exceeds the
US Food and Drug Administration recommended intake of 6 g/day and possibly exceeds physiological need
by as much as 8 g/day.55 This excessive intake is likely
due to the stimulation of putative reward pathways in
the brain provided by sodium stimulation of the “salty”
taste buds on the tongue.55–57 Dopaminergic signaling
such as that observed in other reward-associated behaviors (i.e., overeating and drug use) has been implicated
in the hedonic ingestion of sodium.58,59 In general, the
palatability and craving of salt or salty foods is not always associated with physiological need, and variability
in taste-driven sodium ingestion may be affected by genetics, the environment, and/or pathological conditions
(see below).
Variability in sodium intake
Accurately quantifying sodium intake is challenging.
Daily dietary records and answers to questionnaires are
not optimal because of the lack of specificity in tablespoons or grams when reporting salt intake. Urinary sodium excretion is more accurate but primarily reflects
recent sodium intake and disregards nonrenal sodium
losses such as sodium lost in sweat. Further, wide variability in the serum sodium concentration among individuals renders physiological measures of sodium in the
blood unreliable as a measure of consumption.30
Despite the difficulties in precisely quantifying sodium
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intake, it is evident that there is wide variability in sodium consumption among people and across cultures.
While the drive to ingest salt shows little relation to
sodium depletion in humans, salt does become more
palatable as a consequence of sodium loss. Acute sodium depletion associated with rigorous exercise results
in an increased pleasantness rating for beverages that
contain low concentrations of sodium compared with
those without sodium.60,61 Patients with adrenal insufficiency who lose large amounts of urinary sodium report
a specific craving for salty foods.62 Similarly, sodium
depletion induced by chronic low-sodium diets or loop
diuretics increases the preference for, and the pleasantness rating associated with, salty foods.63,64 Although
these cravings share some common characteristics with
the biological definition of a sodium appetite in animals, humans lack other key features of a true salt appetite. The pleasantness associated with salt ingestion in
humans is limited to sodium chloride ingestion, is specific to salt on foods and in very low concentrations in
beverages, and is likely associated with reward pathways
tied to stimulation of salty taste buds on the tongue.
To the latter point, oral sensory phenotype contributes to variability in human salt intake only indirectly
by influencing “liking” of salty foods. There are 2 common markers of variation in taste and oral sensation:
the perceived bitterness of propylthiouracil (PROP) and
the density of fungiform papillae on the tongue. People
with heightened PROP bitterness can perceive sugars as
sweeter, other bitters as more intense, and dietary fats
as more creamy and/or viscous than individuals who
taste PROP as weakly bitter. These individuals report an
enhanced preference for foods and drinks as they become saltier, as saltiness masks bitterness in the perception of taste. People with a high density of fungiform
papillae have a genetic propensity to experience the
most intense sensations from taste. Those with a high
density of fungiform papillae demonstrate a decreased
preference for high-fat, high-salt foods, as these tastes
may be too intense.65 Collectively, PROP bitterness rating and fungiform papillae number independently explain variability in consuming high-sodium foods by
impacting salt sensation and/or liking.66
The magnitude of “need-free” salt intake may be
influenced by prior episodes of sodium deficiency, specifically during neonatal development.67,68 Sodium depletion in utero permanently enhances salt appetite.69,70 In
a similar manner, neonatal and early childhood sodium
restriction contributes to increased sodium appetite and
salt ingestion throughout life (Table 2).69–71 In these instances, excessive sodium intake is not necessarily reflective of restoring sodium balance but rather an increase in
the palatability of sodium or a dysregulation of the mechanisms associated with stimulating sodium appetite.55
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Table 2 Variability in salt intake: developmental factors
Epoch
Prenatal
Event
Maternal vomiting
Contribution
Increased long-term
sodium appetite
Reduced sodium taste
threshold
Neonatal Low serum sodium Increased dietary sodium
(diuretics)
(age 9–22 yr)
Infancy
Vomiting, diarrhea Increased sodium appetite
(age 9–22 yr)
Childhood Learning
Influences lifetime habits
and preferences
Adulthood High-salt diet
Reduce acute voluntary
intake
Increased mineral preference
Low-salt diet
Reduced sodium
preference
Exercise, sweat loss, Acutely increases
hemodialysis
preference
Repeated dehydra- No effect
tion, blood loss
Lifetime
Personality
No effect
Habits
Presence of salt shaker,
small effect
Culture
Influences preferences and
intake
Conversely, periods of sodium depletion in adulthood do not seem to chronically alter sodium “appetite”
in humans.72 These contrary effects of perinatal and
adult sodium depletion suggest that sodium appetite is
established during an early developmental window during which sodium deprivation can contribute significantly to lifelong salt ingestion.40,72 Repeated bouts of
sodium depletion may result in an increased craving for
sodium and enhanced palatability of salt. Long-term sodium restriction in hypertensive patients reduces the
sensory threshold for sodium detection and increases
the pleasantness ratings of salty foods.64 However, it remains unclear if spontaneous salt-ingestive behaviors
are stimulated by the same neural circuits that are
responsible for sodium “liking.”
The variability in sodium intake and gustatory pleasure associated with sodium ingestion also appears to be
influenced by genetic factors. Data from the Korean
Healthy Twin Study suggest that genetic predisposition
may contribute to behaviors associated with sodium intake.73 In this twin/family cohort study, half-day urine
samples from 162 pairs of twins (133 monozygotic, 29 dizygotic) and 880 singletons were collected to assess 24hour sodium intake; daily sodium intake, sodium density
per calorie, and salt habit questionnaire data were also
collected. In this sample, genetics explained approximately 34% of the variance in total sodium intake.
Monozygotic twins had a higher intraclass correlation
for sodium intake compared with other groups.73
Interestingly, dizygotic twins also demonstrated a higher
correlation for sodium intake compared with nontwin
siblings, suggesting that sharing a neonatal environment
80
and/or closely shared early infant experiences also influence sodium consumption throughout adulthood.
Interestingly, sharing a current residence without
being a family member explained approximately 22% of
the variance in sodium density per calorie consumed,
and spouses showed higher correlations for sodium intake and salt habit than siblings or parent–offspring
pairs.73 While these data suggest there appears to be a
heritability component to quantitative salt intake, environmental exposure to sodium, e.g., availability and
types of foods, use of salt at the table also likely contributes to variability in salty taste perception and lifelong
sodium intake.74–76
Variability in sodium appetite and salt intake is
also affected by cultural (and possibly interrelated environmental) factors. Sodium intakes of different populations around the world vary considerably, with reported
values as low as 0.06 g of salt per day among the
Yanomamo Indians of Brazil77 to 27 g of salt per day in
the Akita prefracture of northeastern Japan.78 More recently, the INTERMAP study (INTERnational collaborative study of MAcronutrients, micronutrients and
blood Pressure), which provided standardized data on
sodium intake and 24-hour urinary sodium excretion in
China, Japan, the United Kingdom, and the United
States, found a 2-fold increase in sodium ingestion in
Northern China and Japan compared with the United
States and the United Kingdom.79 These differences
among cultural groups reflect variability in sodium content in commonly available foods. In European and
North American countries, approximately 75% of sodium comes from preprepared foods and foods eaten
away from the home. In Asian countries, approximately
75 % of sodium in the diet can be attributed to the use
of salt during cooking and from salty sauces such as soy
and miso.80 Therefore, genetic, cultural, and environmental factors all appear to play a role in describing the
variability in sodium ingestion among individuals and
groups of people.80 For all countries from which recent
data are available, and across both genders and all age
ranges, dietary sodium intakes are much higher than
the physiological need.
In summary, the mechanisms that regulate the gustatory sensing of sodium and consequent sodium intake
are sufficient to ensure adequate sodium intake, and
preference for salty-tasting foods and beverages often
induces a hedonistic intake of excess sodium above that
required for adequate water balance. In addition to individual differences in the preference for sodium, variability in cultural and environmental factors such as
types of foods available and salt use at the table provides
additional variability in sodium ingestion among individuals and groups of people. Taken together, these factors provide for tremendous heterogeneity in the
Nutrition ReviewsV Vol. 73(S2):73–82
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amount of sodium ingested among individuals. For
each person, the burden is placed on the mechanisms
that mediate excretion of sodium to maintain physiological sodium and water balance.
10.
11.
12.
13.
CONCLUSION
14.
In summary, exquisite physiological regulation of sodium
and water balance is required for the maintenance of homeostasis. These important regulatory mechanisms are
highly interdependent, and both acute and chronic alterations in intake are balanced by appropriate changes in renal output. In healthy individuals, these tightly coupled
mechanisms maintain extracellular fluid volume and tonicity within a narrow homeostatic range by initiating ingestive behaviors and the release of hormones necessary to
conserve water and sodium within the body. Collectively,
the studies in the present review suggest that healthy individuals of all ages are capable of initiating and adjusting
necessary neurohumoral feedback loops that ensure homeostatic regulation of the extracellular fluid. However, in
instances of pathological dysregulation of these sensitive
mechanisms, the resultant hyper- or hypotonicity of the
extracellular fluid may contribute to acute and/or chronic
disease states.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
Acknowledgments
27.
Funding. W.L.K. was contracted and funded by the
European Hydration Institute. He received financial reimbursement for travel and accommodation expenses
and an honorarium from the European Hydration
Institute for his participation in the conference and for
writing this manuscript.
Declaration of interest. The authors have no relevant interests to declare.
28.
29.
30.
31.
32.
33.
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