N U TR IT ION RE S E ARCH 3 2 ( 2 0 12 ) 30 9 –3 1 9

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Diet promotes sleep duration and quality

Katri Peuhkuri⁎, Nora Sihvola, Riitta Korpela

Institute of Biomedicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, PO Box 63, FIN-00014, Helsinki, Finland

A R T I C LE I N FO AB S T R A C T

Article history: Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only
Received 4 October 2011 partially clear and are the subject of intense research. There is increasing evidence showing
Revised 13 March 2012 that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic
Accepted 20 March 2012 studies have demonstrated that those who sleep less are more likely to consume energy-
rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables,
and to have more irregular meal patterns. In this narrative review, we pose the opposite
Keywords: question: can ingested food affect sleep? The purpose of this review is to discuss the
Sleep evidence linking diet and sleep and to determine whether what we eat and what kind of
Diet nutrients we obtain from the food consumed before bedtime matter. In addition, scientific
Food evidence behind traditional sleep-promoting foods such as milk and some herbal products
Nutrients is briefly described. These are reviewed using data from clinical trials, mostly in healthy
Protein subjects. In addition, we discuss the possible mechanisms behind these observations.
Tryptophan Lastly, we summarize our findings that emerging evidence confirms a link between diet and
sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of
serotonin and melatonin, may be the most helpful in promoting sleep. Although there are
clear physiological connections behind these effects, the clinical relevance needs to be
studied further.
© 2012 Elsevier Inc. All rights reserved.

1. Introduction reductions in sleep duration increase, although decline in

Sleep is a physical and mental resting state, in which a person
becomes relatively inactive and unaware of their environ-
ment. The purposes and mechanisms of sleep are only
partially clear and are the subject of intense research [1,2].
Sleep is considered adequate when there is no daytime
sleepiness or dysfunction. The amount of sleep a person
needs varies individually and depends on various factors, one
of which is age. Most adults need about 7 to 8 hours of sleep
per day, but infants and teenagers need more [3]. With age,
sleep latency, sleep arousals, and awakenings as well as
nighttime sleep duration is paralleled by an increase in
napping during the daytime [4]. Sleep is controlled by the
circadian clock, sleep-wake homeostasis, and willed behavior.
Sleep duration can be measured with fairly simple methods.
Subjective methods include a sleep diary and validated
questionnaires, whereas electroencephalogram, polysomno-
graphy, and actigraphy measurements provide more objective
results. Other parameters to define sleep, such as the
subjective experience of sleep quality, are more complicated
because even the term “sleep quality” has not been rigorously
defined [5].

Abbreviations: 5-HTP, 5-hydroxytryptophan; AADC, aromatic L-amino acid decarboxylase; CCK, cholecystokinin; E%, percent of total
energy intake; GABA, γ-aminobutyric acid; LNAA, large neutral amino acid; PYY, peptide tyrosine-tyrosine; REM, rapid eye movement;
TDO, tryptophan 2,3-dioxygenase; TRP, tryptophan.
⁎ Corresponding author. Tel.: +358 9 191 25 366; fax: +358 9 191 25 364.
E-mail address: katri.peuhkuri@helsinki.fi (K. Peuhkuri).

0271-5317/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.nutres.2012.03.009
310 N U TR IT ION RE S EA RCH 3 2 ( 2 0 12 ) 30 9 –3 19
Cross-sectional and epidemiologic studies have demon-
strated connections between sleep duration and diet. Sleep
deprivation can modify dietary choices, and reduced sleep
duration has been associated with both metabolic disorders
and the increased prevalence of obesity [3]. Adequate sleep is
positively associated with health-related behavior such as
adopting a healthy diet. These associations have been shown
in children [6], adolescents [7–10], and adults [11–13]. Those
who sleep less are more likely to consume energy-rich foods,
get higher proportions of calories from fats or refined
carbohydrates, consume lower proportions of vegetables and
fruits, and have more irregular meal patterns and consume
snacks more often than those sleeping more.
Sleep has an influence on meal patterns, but even the
timing of meals may influence sleep. It is well documented
that individual eating episodes are highly interrelated; thus,
the timing of the previous meal and the resulting satiety
largely determine the time and size of the following meal [14].
The incidence and prevalence of skipping breakfast are
typically higher in persons with low sleep duration than in
those with normal sleep duration [15,16]. Low sleep duration is
especially typical in subjects with nocturnal lifestyles who
replace meals with snacks and who consume most of their
food in the later evening and at night. Thus, they are not
hungry in the morning and replace breakfast with an early
morning snack. As a matter of fact, a regular habit of snacking
is associated with shorter sleep duration [16]. Interestingly,
very long sleep duration is also associated with an unconven-
tional eating rhythm [16]. Because snacking is generally found
to indicate a nutritionally poor and energy-rich diet [17], the
observed association between meal patterns and sleep may, at
least partially, be due to the quality of diet, that is, an absence
of nutrients or excessive amounts of energy-rich foods.
Despite methodological differences, almost all of the
previously mentioned studies indicate that an unhealthy
diet is associated with shorter sleep duration and irregular
sleeping patterns. These studies, however, do not reveal
whether compliance with a recommended diet results in
better sleep or vice versa—whether sleep-deprived people eat
more unhealthy foods just because they are too tired to
follow recommendations.
Both epidemiologic and methodological studies indicate a
relationship between sleep and health [18,19]. However, little
is known about the impact of diet and nutrients on sleep—
that is, whether what we eat and what kind of nutrients we
obtain from the food we consume before bed are of any
consequence. Because there are no recent overviews on the
effects of diet on sleep [20–24] and there are interesting new
publications on the topic, this narrative review aims to
provide an overview of clinical studies, mostly on healthy
humans, to clarify whether the duration or quality of sleep is
associated with the quality of diet or the intake of energy,
carbohydrates, proteins, fats, or other nutrients. However, we
will mostly concentrate on the impact of diet on sleep
duration, which is fairly simple to measure reliably, and the
results are more comparable as compared with measure-
ments of sleep quality, which is an even more complex
phenomenon. Lastly, we will discuss the need and directions
of future research in this area. Effects of drugs, drug-like
products such as melatonin supplements, or other intoxicants
such as alcohol are excluded from this overview. We used the
electronic bibliographical database PubMed until March 2012
(without any methodological restrictions) to identify studies
using the following keywords: sleep, diet, nutrient, energy,
carbohydrate, protein, tryptophan (TRP), fat, vitamin, and
mineral. In addition, we reviewed the references of identified
studies and of selected narrative review articles.
2. Diet and chronotype
The term “chronotype,” also referred to as the circadian type, is
used to characterize sleep patterns. There are 3 main
chronotypes: morning, evening, and midrange [24]. These
individual differences are, in part, heritable, but additional
factors such as cultural and environmental influences mod-
ulate chronotype.
As reviewed previously, nutrients such as glucose, amino
acids, sodium, ethanol, and caffeine, as well as the timing of
meals, can reset the bodily rhythms of rodents [25]. Evidence in
clinical studies of humans is scarce. Kräuchi et al [26] showed
that a single carbohydrate-rich meal may have the capacity to
entrain human circadian rhythms, especially through periph-
eral oscillators, measured as changes in core body temperature
and heart rate. Unfortunately, this interesting study presents
no data on sleep patterns. The intake of certain nutrients and
foods differed significantly by chronotype, which was assessed
by the midpoint of sleep in more than 3000 young Japanese
women [27]. A late midpoint, that is, the evening type, was
associated with energy intake from alcohol, fat, confections,
and meat. By contrast, the morning chronotype was associated
especially with a greater intake of calcium and vitamin B6, as
well as eating more vegetables and pulses. Fleig and Randler
[28], on the other hand, found no relationship between
chronotype and the intake of sweets, vegetables, salad, or
meat but, instead, noticed that later bedtimes and rising times
were associated with a tendency to drink caffeinated drinks,
eat fast food, and consume fewer dairy products.
To conclude, even if clinical evidence of an association
between the human chronotype and diet is lacking, results from
cross-sectional studies and animal models at least suggest that
morning-oriented people tend to have a healthier and more
regular lifestyle compared with evening-oriented ones.
3. Traditional sleep-promoting foods
All nations around the world have traditions regarding the
specific foods that are served to promote healthy sleep. In
many Western countries, for example, cow's milk has
traditionally been considered a tranquilizing beverage with
sleep-inducing capacity. Study conducted almost 80 years ago
reported adults consuming a meal of corn flakes and milk to
exhibit a stronger tendency toward uninterrupted sleep [29].
Forty years later, in an open study using electrophysiologic
recordings in a sleep laboratory, other researchers found
improvements in sleep in terms of duration and a reduced
number of awakenings in 18 older people who ingested milk
fortified with Horlicks powder, a malted barley and wheat, at
bedtime, and reported the action of the fortified milk to be
 N U TR IT ION RE S E ARCH 3 2 ( 2 0 12 ) 30 9 –3 1 9
more effective with serial administration [30]. A modest effect
of milk and Horlicks powder, observed by camera recordings,
was also noticed in 4 healthy male students with no sleeping
problems [31]. More recently in elderly subjects, a daily dose of
100 g or a large dose of 500 g of normal commercial milk had
no effect on sleep or alertness the following morning [32,33].
On the other hand, when commercial milk was replaced with
melatonin-rich nighttime milk in a double-blinded study,
morning activity, reflecting better sleep and rest during the
previous night, was significantly increased in 80 elderly
subjects [32]. Melatonin is a natural compound in cow's
milk, but its concentration increases significantly if cows are
milked in darkness at nighttime. Similarly, when Lactobacillus
helveticus–fermented milk was used in another double-blinded
study, sleep efficacy was improved and the number of
episodes of awakening was reduced, which were measured
by means of actigraphy and a sleep questionnaire (n = 29) [33].
Supplemented probiotics, however, had no effect on sleep in
75 healthy volunteers with symptoms of stress [34].
Other examples of sleep-promoting foods include herbal
products and certain fruits. The use of herbal products such as
chamomile tea to improve sleep is common [35], even if robust
scientific evidence supporting this is, in many cases, nonex-
istent, as reviewed recently [36,37]. In addition, there are
recent reports indicating that certain fruits such as tart
cherries or kiwifruits promote sleep. A double-blinded pilot
study showed that fresh tart cherry juice, consumed twice
daily, produced reductions in insomnia in 15 elderly subjects,
and the time required to fall asleep was reduced by 17 minutes
[38]. The researchers found, however, no influence on any
other sleep parameters during the 2-week clinical trial
compared with a placebo beverage. The influence of cherries
was also noticed in another study of 6 middle-aged and 6
elderly Spanish volunteers [39]. Daily doses of different cherry
cultivars increased sleep time significantly and reduced the
number of awakenings measured by actigraphy compared
with baseline measurements. Another recent study demon-
strated that consuming 2 kiwi fruits an hour before bedtime
improves sleep, both the total sleep time as well as sleep
efficiency during a 4-week open clinical trial with 24 healthy
subjects wearing an actigraphy watch [40].
Clinical evidence for the sleep-promoting effects of the
previously mentioned products is mostly based on individual
studies and is, unfortunately, mainly done with small study
populations. These observations remain to be confirmed, and
the mechanisms remain to be clarified.
4. Energy and macronutrients
The number of clinical trials to explain how the nutrient
content of a single evening meal or the diet of the preceding
day affects the parameters of sleep of the following night is
low. Postprandial clinical trials have mainly focused on
sleepiness or daytime naps shortly after breakfast or lunch.
The effects of lunch and no-lunch conditions on postprandial
afternoon napping measured by polysomnography recordings
were compared in 2 clinical trials in young men with normal
sleeping habits [41,42]. Lunchtime food (n = 12) or an altered
energy content of a midday meal (n = 21) did not promote
311
the initiation of sleep, but eating a meal increased the duration
of sleep episodes more than 3-fold if an afternoon nap was
taken. Furthermore, the macronutrient content of the daytime
meal does not seem to have a notable influence on postpran-
dial sleepiness recorded by polysomnography in 10 to 16
subjects [43,44]. Instead, only a trend toward sleepiness after a
high-fat, low-carbohydrate morning meal compared with a
low-fat, high-carbohydrate meal was noticed in 18 healthy
volunteers [45]. A low-protein, high-carbohydrate breakfast
induced more drowsiness according to sleep diaries in 21
young men, which gave the researchers reason to speculate
that a high concentration of proteins may increase postpran-
dial alertness [46].
In addition to the aforementioned influence of daytime
eating and drowsiness, the influence of food is a more relevant
question for nighttime sleep because night is the principal
time of rest for most people. However, the number of studies
focusing on this is even more limited. Higher-energy intake at
the evening meal extended the sleep duration by 1.4 s/kJ in
healthy toddlers (n = 594) [47]. Nevertheless, no significant
differences in any of the subjective or objective sleep
parameters recorded in sleep laboratory by polysomnography
between a fast (no meal), a high-energy meal (11.9 MJ) and a
normal, control meal (5.7 MJ) 2 hours before going to bed were
observed in 7 adults [48].
In a cross-sectional design, teenage girls who slept less than
5 hours per night were observed to get about 420 kJ more energy
from carbohydrates than those who slept more (n = 126) [10], but
in other studies, adolescents of roughly the same age (n = 240)
and adults (n = 2828) sleeping more than 9 hours per night
consumed more energy from carbohydrates than those sleeping
less [8,13]. In toddlers, the intake of carbohydrates was
accompanied by longer sleep duration (0.8 min/g) [47]. No clinical
trials seeking to measure the impact on sleep duration caused by
the carbohydrate content of an evening meal were found.
However, all other sleep parameters except duration may
be influenced by the total amount of carbohydrates. In
8 healthy young males, a high-carbohydrate, low-fat meal
reduced deep slow-wave sleep (non–rapid eye movement
[non-REM] sleep) and increased the proportion of REM sleep
compared with normal-balanced or low-carbohydrate, high-
fat diets [49], which was confirmed later with 6 subjects [50],
both studies using polysomnographic recordings. Also, a diet
very low in carbohydrates and rich in fat reduced the share
of REM sleep recorded by polysomnography, but also
increased the percentage of deep slow-wave sleep compared
with a control diet high in carbohydrates and low in fat [51].
In this study protocol with 14 subjects, however, it was not
possible to conclude whether the improvement of the quality
of sleep was due to a reduced percentage of carbohydrates
(<1% vs 72% of the total energy intake [E%]) or an increased
percentage of fat (12.5 E% vs 61 E%) or proteins (15.5 E% vs
38 E%). Either way, the researchers speculated the difference
to be linked to the metabolism of dietary fat and after the
release of cholecystokinin (CCK) corresponding to previous
observation by Wells et al [45].
Dietary carbohydrates contain a large variety of sugar
chains with different metabolisms. Thus, it is not surprising
that the amount of any individual carbohydrate has no
consistent influence on sleep parameters. As shown in the
312 N U TR IT ION RE S EA RCH 3 2 ( 2 0 12 ) 30 9 –3 19
aforementioned cross-sectional study of toddlers, the con-
sumption of foods with high Glycemic Index was accompanied
by longer sleep time (1.3 min/g) [47]. However, in a clinical trial
of 12 healthy young men consuming carbohydrate meals with
high or low glycemic loads, profiling the type of carbohydrate
ingested, did not affect sleep duration or any other sleep
indexes according to polysomnographic recordings, except for
the onset of sleep [52]. The study noticed shortened sleep-
onset latency by approximately 10 minutes after a carbohy-
drate-rich evening meal with a high Glycemic Index compared
with a low-index meal, suggesting a difference between the
carbohydrates. The carbohydrate content of these rice-based
meals was more than 90% of the total energy content, and the
meals were ingested 4 hours before bedtime.
Clinical trials assessing the impact of other macronutri-
ents, that is, proteins and fats, on sleep duration are scarce.
Clinical trials show some support that protein fragments or
amino acids, when administered in pharmacologic doses,
may have sleep-promoting influence. Supplemented TRP is
being used as a sleep aid, even if the clinical evidence is
challenged, as reviewed previously [53,54]. Tryptophan is a
precursor to the neurotransmitter serotonin and the neuro-
secretory hormone melatonin, both of which are linked to
sleep and alertness [1,2]. In a study using polysomnographic
equipment on 17 healthy volunteers, TRP depletion pro-
duced by a 48-hour low-protein diet increased REM sleep
latency by 21 minutes, but no effect on sleep duration or
non-REM sleep was noticed during the following nights'
sleep [55]. Regardless of the above finding, as little as 250 mg
of pure pharmaceutical-grade TRP has improved sleep in
people with sleeping problems [53,54].
As part of the diet, the metabolism of TRP is more
complicated. Protein-sourced TRP (de-oiled butternut squash
seeds) was compared with pharmaceutical-grade TRP in a
health bar containing carbohydrates and vitamins [56]. A
trend toward an increase in the total sleep time of about 19
minutes (5.5% increase) was observed with protein-sourced TRP
in a placebo-controlled study of 49 subjects meeting the criteria
for insomnia. α-Lactalbumin, one of the primary milk proteins,
is a good source of TRP. An α-lactalbumin–rich evening meal,
however, did not induce feelings of sleepiness measured by
electroencephalographic recordings in a sleep laboratory study
of 14 healthy subjects with mild sleep complaints, although all
subjects felt more alert the next morning compared with when
they were administered the placebo meal [57].
According to cross-sectional studies, the influence of
dietary fat on sleep duration is conflicting. In small children
(n = 594), teenage girls (n = 126), and in a small study of 30
Greek women, a trend was observed toward longer sleep
duration, with subjects consuming more energy from fat,
whereas in other large studies with adolescents (n = 240) and
adults (n = 459 and n = 2828), short sleep duration was
correlated with increased fat intake [8,10–13,47,58]. Studies of
high-fat, low-carbohydrate diets have not observed marked
differences but only a remote trend on sleep duration, but also
some influence on the relation of non-REM and REM sleep as
described above [45,49,51]. Very long-chain fatty acids play an
important role in the pineal gland and the production of
melatonin [59]. Despite this clear biological connection to
sleep, no improvement either in subjective or objective
parameters of sleep or secretion of melatonin was noticed in
more than 100 adults with chronic insomnia after supple-
mentation with polyunsaturated fatty acid capsules [60].
To conclude, regarding the influence of energy and
macronutrients on sleep, clinical interventions confirm the
cross-sectional observations that there is a connection
between the intake of macronutrients and sleep. Although
the number of studies is small and definite differences in
designs and methods exist, the macronutrient content of a
diet or evening meal seems to modify sleep duration at most
only 10 minutes in healthy subjects with no sleep problems.
Carbohydrates and fats, at least in large quantities, may
modulate sleep quality by influencing the ratio of REM and
non-REM sleep. Of proteins, amino acid TRP is the most
promising candidate as a sleep-promoting nutrient at least
with pharmacological doses.
5. B vitamins and magnesium
Deficiencies of group B vitamins and minerals may disrupt
sleep. Their effect seems to be based on their influence on the
secretion of melatonin. Melatonin is a hormone secreted
naturally by the pineal gland, especially at night. In several
studies, pharmacological doses of melatonin have been found
helpful in inducing and maintaining sleep both in children
and in adults with normal sleep patterns and those having
insomnia [61,62]. However, the effect of melatonin is most
apparent only if a person's melatonin level is low.
The secretion of melatonin is influenced by some external
factors such as artificial light. Vitamin B12 contributes to
melatonin secretion [63]. Treatment with varying doses of
vitamin B12 has a potentially beneficial effect on the sleep-
wake rhythm and in delayed sleep-phase syndrome in
healthy subjects measured by actigraphy equipment (n = 20)
[64] and sleep diary (n = 102) [65] and in patients with
Alzheimer dementia using actigraphy recordings (n = 28)
[66], although conflicting results exist [67]. No clear benefit,
however, has been reported in sleep duration.
Some clinical evidence substantiates the influence of other
group B vitamins on sleep. Administration of nicotinamide
(niacin) to 6 people with normal sleep pattern increased REM
sleep, and when given to subjects with moderate to severe
insomnia, the sleep efficacy, recorded in a sleep laboratory
using electroencephalogram, was improved [68]. Niacin is
biosynthesized from dietary TRP via the so-called kynurenine
pathway. The researchers speculate that administration of
niacin results in the buildup of nicotinamide adenine dinucle-
otide, which may reduce the amount of TRP converted to
niacin, thus leaving TRP available to the synthesis of serotonin
and melatonin.
Vitamin B6, pyridoxine, is needed in the synthesis of
serotonin from TRP. 5-Hydroxytryptophan (5-HTP), which is
an intermediate in this process, is converted to serotonin by
an enzyme called aromatic L-amino acid decarboxylase (AADC)
[69]. Aromatic L-amino acid decarboxylase is a pyridoxal 5′-
phosphate–dependent enzyme, and pyridoxine is a precursor
for pyridoxal 5′-phosphate. Despite the clear physiological
connection between dietary pyridoxine and melatonin secre-
tion, no effect on sleep using polysomnographic recordings
 N U TR IT ION RE S E ARCH 3 2 ( 2 0 12 ) 30 9 –3 1 9
was observed after evening treatment with oral pyridoxine
either on melatonin secretion or on sleep duration in 12
healthy men compared with the placebo capsule [70]. In a
preliminary placebo-controlled double-blind study, however,
pyridoxine was found to increase cortical arousal during REM
sleep and to increase the vividness of the dreams of 12 college
students [71], thus demonstrating some influence on sleep.
A relationship between the concentration of magnesium in
the blood and sleep has been suggested [72–74]. This
documentation is based mostly on experimental models
with rodents, and clinical evidence is scarce. Nonetheless,
oral magnesium supplementation has improved sleep quality
and total sleep time recorded by polysomnography in 2
separate studies with about 10 subjects with low magnesium
status [75,76]. Rondanelli et al [77] found a preparation
containing melatonin, magnesium, and zinc taken daily for
8 weeks 1 hour before bedtime to improve sleep quality and
total sleep time recorded by wearable armband-shaped sensor
in 43 elderly subjects with primary insomnia compared with a
placebo capsule. This is believed to be based on magnesium
enhancing the secretion of melatonin from the pineal gland
by stimulating serotonin N-acetyltransferase activity, the
key enzyme in melatonin synthesis [36], and it being a
γ-aminobutyric acid (GABA) agonist [74,75]. γ-Aminobutyric
acid is the main inhibitory neurotransmitter of the central
nervous system, and it is well established that activation of
GABA(A) receptors favors sleep. To be precise, many hypnotic
drugs and anesthetics enhance GABA-mediated neurotrans-
mission. Magnesium sulfate has shown a GABA-agonistic
effect on sleep in 10 healthy men, even if no effect on
melatonin release was observed [78,79].
To conclude, nutritional deficiencies such as that of
magnesium or group B vitamins may impair sleep. There is
Fig. 1 – Dietary factors promote sleep via circulating intestinal hormones, by stimulating the synthesis of serotonin and
melatonin, acting on GABAergic or serotonergic neurons or via other unidentified mechanisms.
313
evidence of a modest influence of group B vitamin and
magnesium supplementation on sleep and, more clearly, on
sleep quality and the regulation of sleep-wake rhythm than on
sleep duration. Physiologically, this is based on the mediation
of neurotransmission by interacting in the synthesis of
serotonin and melatonin.
6. Possible mechanism for the relationship
between diet and sleep: sleep-promoting and
wake-promoting substances
Sleep is an active process that requires the participation of a
variety of brain regions. The daily cycle of sleep and
wakefulness is regulated by various hormones produced by
the hypothalamus and external stimuli, with the amount of
light being the most obvious example [1,2]. Nerve-signaling
chemicals or neurotransmitters control whether we are asleep
or awake by acting on different groups of nerve cells in the
brain. Many sleep-promoting substances have been identified,
and they can be divided into 2 basic groups: wake-promoting
neurochemical factors including noradrenalin, serotonin,
acetylcholine, histamine, and orexin and the sleep-promoting
system including GABA, adenosine, and nitric oxide, as
reviewed recently [1,2]. In general, sleep can be promoted
either by inhibiting wake-promoting mechanisms or by
increasing sleep-promoting factors either by dietary or by
other means (Fig. 1).
6.1. The role of intestinal peptide hormones and sleep
Food intake induces the release of various gut hormones
affecting local sites or circulating in the blood and signaling
314 N U TR IT ION RE S EA RCH 3 2 ( 2 0 12 ) 30 9 –3 19
via vagal nerve afferents that communicate with the hypo-
thalamus and the brain. Some reports have demonstrated
various appetite-modulating substances such as CCK, ghrelin,
and peptide tyrosine-tyrosine (PYY) to have a significant effect
on sleep. In addition to these, there are other neuropeptides
acting both in the gut and in the brain, such as vasoactive
intestinal polypeptide, with known influence on intestinal
physiology and sleep regulation [80].
Dietary fats and proteins and, to a much smaller extent,
carbohydrates stimulate the release of CCK from mucosa
cells in the duodenum and the jejunum. Cholecystoki-
nin regulates gut motility and stimulates the delivery of
digestive enzymes from the pancreas and the gallbladder.
Cholecystokinin is also produced in the enteric nervous
system and is abundantly distributed in the brain as well
[81]. The postprandial release of CCK induced sleepiness
in healthy adult volunteers 2 to 3 hours after a high-fat,
low-carbohydrate meal [45]. The nutritional composition
of the served test meal was, however, far from a normal
Western diet containing 74 E% from fat and only 19 E%
from carbohydrates.
Ghrelin is mostly known to stimulate appetite and plays a
role in energy balance. In addition, during the last decade,
various studies have been published, showing its effects on
sleep-wake behavior, as reviewed recently by Steiger et al [80].
It seems that ghrelin stimulates the activity of the somato-
tropic and the hypothalamic-pituitary-adrenal axis affecting
concentrations of growth hormone and cortisol, which both
are involved in sleep regulation. The influence of ghrelin on
sleep seems to be more obvious in men [82].
Peptide tyrosine-tyrosine is one of the major components
of the gut-brain axis. It is released from the gastrointestinal
tract postprandially in relation to the energy content of a
meal. After its release, PYY can cross the blood-brain barrier
and act on the central nervous system. In animal experiments,
nocturnal intraperitoneal administration decreased wakeful-
ness and enhanced non-REM sleep [83]. The precise mecha-
nism is not clear, but the relationship between serotonin and
PYY is believed to exist [84].
It is known that secretion of gastrointestinal regulatory
peptides is not affected by sleep [85], but it is not certain
whether naturally secreted gut peptides induce or modify
sleep. Observations have been made mainly in rodents and
by using intraperitoneal or intravenous administration of
gut peptides. Further studies are needed to verify whether the
natural release of peptide hormones by dietary modulation
has a role in sleep regulation.
6.2. Dietary TRP as a precursor for serotonin
and melatonin
The commonly discussed mechanisms increasing sleep
duration are the ways to promote the synthesis of serotonin.
Serotonin is a neurotransmitter that relays information to
different parts of the brain, regulating many of the vital
systems in the body, as reviewed previously [86–88]. In
addition, serotonin controls most brain functions such as
sleep cycles either indirectly or directly [1,2]. Generally,
serotonin promotes consciousness and suppresses sleep, but
there are at least 15 different serotonin receptors with varied
effects after serotonin binding. Together, these serotonergic
neurons innervate many brain regions that influence sleep-
wake behavior. One of the most potent ways for serotonin to
regulate sleep is through changes in melatonin concentration
because serotonin is an intermediary product in the produc-
tion of melatonin, as shown in Fig. 2.
Some foods contain melatonin and serotonin as such.
They have been detected in a considerable variety of plant
species including roots, leaves, fruits, and seeds [89]. These
foods may also contain TRP. There is no clear evidence of the
clinical importance of food-based melatonin on sleep, but
supplemented melatonin is absorbed and can be released into
circulation, thus increasing the plasma concentrations of
melatonin [90].
More evidence on the influence of nutrients on the
synthesis of serotonin is available (Fig. 2). Tryptophan is a
precursor of serotonin, and increased TRP levels in the brain
induce the synthesis of serotonin. The traverse of dietary TRP
through the blood-brain barrier is favored by a higher plasma
concentration of TRP in comparison with the other competing
large neutral amino acids (LNAAs). It is known that the plasma
TRP/LNAA ratio is affected by both dietary carbohydrates and
dietary proteins [91]. Proteins rich in TRP, such as α-
lactalbumin, increase the plasma TRP/LNAA ratio up to 130%
and increase brain serotonin concentration [57]. However, if
the diet contains plenty of other LNAAs, TRP transport
through the blood-brain barrier is reduced. Thus, to increase
the availability of TRP in adequate amount, the addition of
dietary proteins containing TRP may not be the only or even
the most effective way.
Insulin release from the pancreas is promoted, especially
by the presence of carbohydrates in the gut lumen. The
effect of insulin on drowsiness is not fully understood.
Insulin has an influence on the transport of TRP after a
carbohydrate-rich meal [56]. A high postprandial level of
insulin after a carbohydrate load favors the transport of
TRP to the brain because being a powerful anabolic agent,
insulin either inhibits peripheral amino acid release or
promotes the peripheral uptake of the other LNAAs.
Thus, in response to an increasing plasma glucose concen-
tration after a carbohydrate load, insulin mediates the
uptake of LNAAs into muscle but not TRP, which is largely
bound to plasma albumin. Consequently, the TRP/LNAA
ratio remains high, and the concentration of other compet-
ing LNAAs is reduced [91,92]. A dose-response curve for
glucose to increase the serum concentration of TRP in com-
parison with other LNAAs has been discovered [93,94].
Meals high in protein usually result in a less pronounced
postprandial insulin increase compared with high-carbohy-
drate meals [91].
Some vitamins may promote the availability of TRP for
serotonin synthesis. Vitamin B3, or niacin, suppresses the
activity of tryptophan 2,3-dioxygenase (TDO), known also as
TRP pyrrolase, which is one of the key enzymes in the
conversion of TRP to niacin (nicotinic acid). If TRP is converted
to niacin, it will not be available as a precursor to serotonin in
the brain, and thus, supplementation with vitamin B3 can
reduce the “loss” of TRP to nicotinic acid. Vitamin B6,
pyridoxine, is needed by AADC, which, in turn, is required to
convert 5-HTP to serotonin, as described previously.
 N U TR IT ION RE S E ARCH 3 2 ( 2 0 12 ) 30 9 –3 1 9 315

Fig. 2 – Possible mechanisms of the influence of dietary components on the synthesis of serotonin and melatonin. A, Diet as a
source of TRP: TRP is metabolized in the brain along different pathways to serotonin, melatonin, and niacin and partly used as a
source of protein synthesis. B, Dietary influence on TRP transport to the brain: other dietary components such as carbohydrates
and other LNAAs affect the intensity of TRP in crossing the blood-brain barrier. C, Stimulating the synthesis of serotonin and
melatonin: 5-HTP is converted to serotonin by an enzyme, AADC, which needs pyridoxine (vitamin B6), and enzyme
arylalkylamine-N-acetyltransferase (NAT) which needs n-3 fatty acids. D, Availability of TRP to the synthesis of serotonin and
melatonin: TDO is an enzyme that catalyzes the chemical reaction of TRP to formylkynurenine, which is rapidly converted to
kynurenine and, finally, to niacin. Niacin (vitamin B3) suppresses the activity of TDO, thus leaving more TRP to be used in the
synthesis of serotonin.

6.3. Other possible mechanisms related to dietary proteins
and nucleotides
Proteins exert a wide range of nutritional, functional, and
biological activities. Some of them have sequences posses-
sing specific biological properties that make these fragments
potential ingredients of health-promoting foods, as reviewed
by Kekkonen and Peuhkuri [95]. Bioactive peptides may be
released after enzymatic digestion either in the gastrointes-
tinal tract or during industrial processes. Bioactive pep-
tides may enter peripheral blood and exert systemic effects,
or exert local effects in the gastrointestinal tract. In adults,
intestinal mucosa acts as an efficient barrier between
luminal contents and the systemic circulation. However,
bioactive peptides have been found in the blood of adult
humans after ingestion [96]. Thus, it is possible that
relatively large bioactive peptides can cross the adult
digestive endothelium in significant amounts.
Increasing attention is focused on milk-based bioactive
peptides including peptides with opioid and opioid antagonist
activities that may have a functional role by interacting with
the endogenous opioid system [97]. Some of them have been
associated with a slight impact on sleep. α-s1-Casein hydro-
lysate, for example, exhibits a benzodiazepine-like activity on
the GABA(A) receptor [98]. Other bioactive peptides may also
be related to GABAergic or serotonergic neurons and, thus,
regulate sleep, but this remains to be studied.
The nonprotein nitrogen fraction of diet includes food-
based DNA and RNA as well as nucleotides and their
fragments. Nucleotides are building blocks of nucleic acids
responsible for storing and transmitting genetic information.
It is estimated that depending on diet, the daily amount of
DNA-originated fragments may be 1 to 2 g [99]. The more
processed food humans consume, the fewer untouched cells
containing nucleotides exist in the diet.
Adenosine 5′monophosphate is considered as an endoge-
nous sleep factor [100] partly because of the well-known
mechanism of caffeine as an adenosine receptor antagonist.
Another nucleotide, guanosine 5′monophosphate, stimulates
the secretion of the sleep-hormone melatonin via the secondary
messenger cyclic guanosine monophosphate-including nucle-
otide parts. Nucleotides are naturally present in breast milk, and
improved sleep (after orally dosed nucleotides) has been studied
mainly in infants [101–103]. However, the relevance of dietary
nucleotides in promoting sleep in adults can be questioned
because the endogenous liberation of nucleotides exceeds
the amount of absorbed dietary nucleotides [99].
To conclude, there are several possible mechanisms that
mediate the influence of nutrients on sleep. The principal
route seems to be via the production of serotonin and
316 N U TR IT ION RE S EA RCH 3 2 ( 2 0 12 ) 30 9 –3 19
melatonin. In addition, ingested food induces local secretion
of many intestinal peptides such as CCK, some of which are
known to slightly mediate sleep as well. Bioactive peptides or
the nonprotein nitrogen fraction of diet may promote sleep
even if the clinical relevance of these findings requires
further investigation.
7. Future challenges in diet and sleep research
The amount and quality of sleep have an enormous impact
on daily life. Disordered sleep affects work, concentration,
and ability to interact with others. Because the need for sleep
varies individually and longer sleep duration does not
necessarily lead to alertness in the morning, sleep duration
is a robust way to describe sleep, especially if it is
determined only with subjective questionnaires and sleep
diaries. More objective and sophisticated methods to esti-
mate sleep are definitely needed to demonstrate slight
nutritional nuances both in sleep duration and its quality
in healthy subjects.
There are still large uncertainties regarding the associ-
ation between diet, the intake of nutrients, and sleep both
in duration and in quality. The evidence presented is
mostly based on small individual studies, which remain
to be confirmed with large populations and subgroups such
as subjects with sleep problems. Furthermore, there is a
clear need for clinical trials with objective methods to
measure sleep, confirming the cross-sectional and epide-
miologic observations.
8. Conclusions
In this review, we discussed studies to illustrate the complex
interaction between diet and sleep. Although concrete clinical
relevance has yet to be established, emerging evidence
suggests a link between nutrients and sleep. Studies to
prove the effects of both macronutrients and micronutrients
on sleep parameters, however, are limited by small numbers
of participants and varied designs and methods.
Whether ingested food directly affects sleep is difficult to
address because the extent to which diet and nutrients can
boost sleep remains unclear. Eating the right combination of
foods before going to sleep and what foods to avoid in the
evening may be beneficial in enhancing sleep. Although
traditional sleep-promoting foods are backed by only limited
clinical evidence, they may be useful in some cases. One such
example is milk, which contains several nutrients with
potential sleep-promoting properties. Tryptophan is a com-
pulsory ingredient for the body to produce serotonin, the
neurotransmitter best known for inducing feelings of calm-
ness and drowsiness. Group B vitamins are also needed in the
synthesis of serotonin. Obtaining an optimal amount of TRP
requires a combination of foods containing TRP with ample
carbohydrates. According to the reviewed studies, a balanced
and varied diet that is rich in fresh fruits, vegetables, whole
grains, and low-fat protein sources (all of which contain
plenty of TRP, as well as group B vitamins, minerals, and
unrefined carbohydrates) can improve sleep. Until further
studies are conducted, this is the best means to address the
issue for the time being.
Acknowledgment
The authors declare no conflict of interest regarding this
review. They have not received any funding or benefits
from industry, but K.P. and N.S. received support from The
SalWe Research Program for Mind and Body (Tekes–The
Finnish Funding Agency for Technology and Innovation
Grant 1104/10).
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