Intermittent drinking, oxytocin and human health
L. Pruimbooma,b,⇑, D. Reheisa
aNatura Foundation, Edisonstraat 66, 3281 NC Numansdorp, Netherlands
bDepartment of Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen, PO Box 30.001, 9700 RB Groningen, Netherl ands
article info
Article history:
Received 25 February 2016Revised 26 April 2016Accepted 26 April 2016
Keywords:
Thirst
Addiction
CravingCollaborationHealthEvolutionOxytocinabstract
Looking at a waterhole, it is surprising that so many animals share the same space without visible signs of
anxiety or aggression. Although waterholes are the preferred feeding locations of large carnivores, water-
holes are shared by all type of herbivores of all sizes and shapes, including elephants. Recent researchshows that the homeostatic disturbances leading to the ‘‘thirst feeling” not only activate speciﬁc sub-stances regulating water and mineral household, but also the ‘‘trust and love” hormone oxytocin, while
decreasing the production of the typical stress hormone cortisol. People using drugs, seem to be in search
for oxytocin, as evidenced in studies with individuals on drugs such as ecstasy and gamma-hydroxybyturate. Hot environment, drought and increased sweating also activate speciﬁc oxytocin-
producing parts of the hypothalamus, just as breastfeeding does in mother andinfant. Water homeostasis
is the only allostatic system activating trust neuro-anatomy and we suggest that this is due to the factthat all animals depend on water, whereas food type is species speciﬁc. Our hypothesis; regulating drink-
ing behaviour through intermittent bulk drinking could increase oxytocin signalling, recover human trust
and increase health by down-regulation of stress axis activity and inﬂammatory activity of the immunesystem. Intermittent bulk drinking should be deﬁned as water (including tea and coffee) drinking up to afeeling of satiety and regulated by a mild feeling of thirst. This would mean that people would not drink
less quantity but less frequently and that’s how all animals, but also human newborns behave. It is the
latter group, which is probably the only group of humans with a normal ﬂuid homeostasis. /C2112016 Elsevier Ltd. All rights reserved. 1. Introduction
Stress, broadly deﬁned as a real or perceived threat to home-
ostasis, activates neural circuits that alter the body’s physiology
and behaviour to ensure survival and well-being. Physical stressors
are real threats that create signals within the internal environment
that communicate deviations from homeostasis to the brain. In
contrast, perceived threats or psychogenic stressors create signals
that arise within the brain itself as it interprets stimuli in the exter-
nal environment as potential insults [1]. Both type of stress factors
activate allostatic systems, including the sympathetic nervous sys-tem and hypothalamic circuits, leading to stressful and even
aggressive behaviour [2]. Starvation, infection, dehydration, vio-
lence and climate are ancient stressors producing severe danger
to the body and have therefore shaped ultimate survival function
producing proximate homeostatic feelings to induce behaviour at
service of the ultimate purpose [3]. Perhaps the best example ishumans crying. The ultimate explanation of crying is that it elicits
care and defence from mothers and other care-givers; if infants do
not cry when in need of assistance, it will be less likely to survive. Proximate explanations include both the external triggers of cry-
ing, for example physical separation from the caregiver, cold, or a
lack of food, and also the internal mechanisms, such as the limbic
system and the endogenous opioids involved in the cessation of
crying. These are proximate explanations because they describe
the immediate causal triggers of crying [4]. In this context, the ulti-
mate explanation for hunger is to signal the body for possible star-
vation and death. The proximate value of hunger is that it leads toeating, although eating is also stimulated by looking at, smelling of
and thinking in food, which are therefore all proximate causes of
eating [5]. This so-called thought-shaped fusion can be so strong
that individuals can gain weight just looking at food [6]. Food deﬁ-
ciency as a stress factor activates a complex systemic response,
which should lead to gluconeogenesis, changes in energy distribu-
tion and spontaneous physical activity [7,8] . Starvation may induce
a certain level of aggressive behaviour, which should be considered
adaptive when hunting big game or when suffering from a lack of
high-energy nutrients [9,10] , whereas food sharing behaviour is
http://dx.doi.org/10.1016/j.mehy.2016.04.043
0306-9877/ /C2112016 Elsevier Ltd. All rights reserved.⇑Corresponding author at: Burgemeester Marijnenlaan 98, 2585 DR Den Haag,
Holland, Netherlands. E-mail address: cpni.pruimboom@icloud.com (L. Pruimboom).Medical Hypotheses 92 (2016) 80–83
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journal homepage: www.else vier.com/locate/mehy
more beneﬁcious once the animal has been hunted (see [11] and
the references herein). Overall, stress responses activate the sympathetic nervous sys-
tem, together with the HPA axis exerting a range of effects in ben-
eﬁt of solving the homeostatic disturbance as fast as possible. Of all
stress factors dehydration occupies a special place in animal evolu-
tion. It seems to be the only homeostatic disturbance leading to
attenuation of stress axis responses, decrease of fear feelings, anx-
iety and aggressive behaviour [12]. Drinking, caused by regulatory
thirst, could be considered proximate behaviour at service of pre-
venting dehydration, an ultimate purpose [13]. Nevertheless it is
regulatory or also physiological drinking, which is regulated by
oxytocin and therefore drinking could also stand at the service of
another ultimate purpose; bonding. These are the reasons which
made us formulate our hypothesis; Could bulk drinking recoverhuman health, trust and mental well being? In this hypothesis
‘‘bulk drinking” is deﬁned as non-frequent drinking up to satiety
and only when thirsty; like drinking visiting a waterhole. 2. Thirst, trust, oxytocin and bonding
Animals drink up to satiety every time they drink, just as infants
do. So infants and animals ‘‘suffer” real thirst (regulatory/physio-
logical thirst, 14) based on hypernatremia, hypovolemia and/or
hyperosmolality [15,16] and these conditions induce increased
oxytocin signalling (Olszewski, 2010). Oxytocin has numerous
effects on multiple physiological mechanisms and oxytocin inﬂu-
ences behaviour signiﬁcantly (see below). The mentioned up to
satiety-drinking behaviour of infants every time they are breast-
fed, is opposite to modern adults who drink small amounts of liq-
uid, often numerous times every day. This latter way of drinking should be considered evolutionary
novel and might affect the water homeostasis and even health
[14]. We think that this constant drinking decreases oxytocin sig-
nalling through chronic low NaCl levels, leading to salt- and sugar
craving, whereas dehydration/hypernatremia increases oxytocin
induced water-craving and inhibition of hunger and carbohydrate
intake [17,18] . Recent research shows that in spite of the expected typical
stress response, mild hypernatremia as a state of dehydration
decreases the activity of the HPA axis (less cortisol production)
and increases the production of oxytocin and arginine-
vasopressin signiﬁcantly [12]. This study further showed that
hypernatremia as a psychogenic/physical stress factor attenuates
the heart limb of the stress response and increases social engage-
ment. Oxytocin and vasopressin are important hormones for devel-
opment of trust, love and bonding neuroanatomy ( [19] and the
references herein). Oxytocin further inﬂuences the immune
response through context-based interactions. It maintains periph-
eral homeostasis during acute inﬂammation [20], has anti-
inﬂammatory protective effects on the heart muscle [21], increases
the production of salivary IgA [22] and has overall anti-
inﬂammatory effects [23]. Breast-feeding is the most signiﬁcant
example of how a homeostatic need induces bonding, in this case
between mother and baby, through the massive release of oxytocin
[24] and affective-bonding mechanisms are responsible for neuro-
anatomical development and immune function later in life [25,26] . It is even so that long term breastfeeding prevents the develop-
ment of criminal and overall anti-social behaviour in later adults
[62]. Paediatricians agree that hydration in children may be optimal
only in breastfed infants. However, their hydration status is very
peculiar. Total water intake per unit of body weight is four times
higher in infants compared to adults. Breast milk has higher water
content per energy unit than the diet of adults. Nevertheless, urinevolume per unit energy is almost identical. Infants retain water for
growth and have higher non-renal water losses due to a higher
body surface area related to body mass. However, osmolar load
per unit of energy is four times lower which corresponds to a very
low urine osmolality of 130 mosm/kg and leaves only a small renal
dilution capacity to excrete an extra water load [27]. Breastfeeding
is normally a topic studied in relationship with eating behaviour,
although we and others [28] think that it much more reﬂects ﬂuid
needs, water and sodium homeostasis. Water is an essential nutrient for all animals and plants across
lifespan and maintaining chronic hydration is recognised to pro-
vide multiple health beneﬁts and enhance quality of life [29]. Mod-
ern diseases are mostly caused by the cause of causes, low-grade
inﬂammation or metaﬂammation [30–32] . The actual environment
seems to be pro-inﬂammatory and the sum of novel anthropogenicfactors, including food and drinking behaviour, might give a plau-
sible explanation for the increase of people suffering from chronic
non-communicable disorders [30,33,34] . Optimal water-intake,
based on a certain rhythm might optimise oxytocin signalling,
recover human character and regulate immune activity [35]. Recent research on the relations of personality to well-being shows
that the people who are most healthy, happy and fulﬁlled are those
who are high in all three of the character traits of self-directedness,
cooperativeness, and self-transcendence as measured by the Temper-
ament and Character Inventory [36]. All three traits are related
with the functionality of oxytocin [37,38] and disruption might
cause pathological dominance of one of them, leading to several
disorders such as autism [39]. We suggest that intra- and inter-
species behaviour at the waterhole could serve as example of
how to recover health, trust and mental well being in and between
modern humans, which is the hypothesis we present in this review
paper. 3. People at search for oxytocin; the pandemic use of oxytocin-
ergic drugs and the need for new interventions; our hypothesis
Prosocial and empathogenic behaviour depend on endogenous
oxytocin systems, which might be disturbed in people engaging
in drug use and addiction [40]. It has been shown recently that
the rate of parental bonding and attachment in childhood is
directly related with adult psychosocial behaviour including drug
use and abuse [41]. It might even be so that drug users become
‘‘bonded” to their drugs and the environmental triggers related
with the use of drugs [40]. On the other hand, stable social bonds and happy relationships,
perhaps associated with higher levels of oxytocin, might be protec-
tive against addiction to drugs [42]. Social reintegration and reha-
bilitation are important factors to promote drug abstinence and
recovery from addiction [43] and family management seems to
be of speciﬁc signiﬁcance [44]. These studies suggest that the role
of oxytocin signalling is central to drug use and abuse and that suc-
cessful interventions should focus on recovery of dysfunctional
oxytocin mechanisms, which perhaps is the secret behind Alco-
holics Anonymous [45] and group therapy [46]. An enormous
amount of young and not so young people are engaging in the
use of a wide range of oxytocinergic drugs such as ecstasy, fantasy,
cannabis and cocaine and not all of them suffered childhood abuse,
lack of parental bonding or neglect (World Drug Report 2012). We
think that they are ‘‘searching” people for normal social interaction
in a society dominated by ‘‘egoistic hawks” and very few social
‘‘doves” [3,47] . As stated by Blum et al. [48]: ‘‘people provide the
real ‘‘highs”. People need people. However, in today’s screwed
up, ﬁnancially unstable (1.4 million bankruptcies 2009), and
very scary world, loneliness and alienation are commonplace. Everything would look perfect if we were all living in a vacuum,L. Pruimboom, D. Reheis / Medical Hypotheses 92 (2016) 80–83 81but instead millions, if they are lucky enough not to be homeless,
are probably living in glass houses vulnerable to being shattered.”
When social interaction, social support and family bonding is
lacking we always have the probability to use synthetic happiness
as fallback strategy. Oxytocin signalling through social interaction
might protect against drug abuse, but if so, water household ther-
apy might do the same thing. Oral and intranasal oxytocin
decreases the use of drugs signiﬁcantly [49], endogenous oxytocin
does the same but also decreases carbohydrate intake [50], regu-
lates the immune system and make people basically cooperative,
trustworthy and prosocial [51]. The pro-social effects of ecstasy
and fantasy, observable in ‘‘house parties”, seem to be produced
by oxytocin pathways and oxytocin signalling might be further
increased by intense sweating during partying, leading to loss of
water and dehydration [52–54] . Oxytocin signalling is further
stimulated when environmental temperature is high [55]. This
could easily explain why the majority of people feel better in a
warm climate when they are on holidays and even seem to be
more empathic and therefore ‘‘oxytocinergic”, knowing that empa-
thy is deﬁnitely an oxytocinergic trait [56]. The warm weather/
oxytocin equation seems clear; high temperature produces sweat-
ing, sweating induces dehydration and dehydration activates oxy-
tocin pathways. Drinking a beer only supports this ‘‘holiday
bonding” feeling by induction of more thirst and dehydration
which can even cause beer intoxication (beer potomania, [57]). Mild thirst induces oxytocin production and oxytocin improves
multiple pathophysiological pathways and therefore it could be the
use of intermittent drinking protocols that helps to solve chronic
inﬂammatory states, bonding disorders and perhaps even addic-
tion; our hypothesis. 4. Discussion
Bulk drinking, earlier deﬁned as non-frequent drinking up to
satiety, resembles the animal behaviour at waterholes. The major-
ity of herbivores travel from waterhole to waterhole to cover their
ﬂuid needs and will drink up to satiety every time they visit this or
another waterhole [58]. Animals at the waterhole show low level
of anxiety and fear and this behaviour is probably caused by
dehydration-increased oxytocin signalling [12]. More speciﬁcally, numerous studies have demonstrated that
oxytocin producing neurons in the hypothalamic supraoptic
nucleus (SON) and the paraventricular nucleus (PVN) are activated
in response to osmotic and volemic thirst and that this results in
secretion of OT into the bloodstream [59–61] . It has long been known that dehydration affects physical and
cognitive behaviour signiﬁcantly, including physical, visuomotor,psychomotor, and cognitive performance [63]. Dehydration can
even affect the cognitive performance of pilots, affecting ﬂight
safety [64]. These dehydration effects are noticeable when people
loose 2% of their bodyweight [65]. It’s clear that these effects are
not at all beneﬁcial for the host, which is further evidenced by
recent research of dehydration consequences caused by the use
of alcohol [66]. Nevertheless it are these effects which makes the need for
water urgent and it could easily be that these effects produce the
observed inhibition of fear and anxiety at psychological level when
people suffer from dehydration. It should further be noted that the
negative effects are observed when people suffer from long term
dehydration (20 h), which is something we do not propose. We
propose a water drinking rhythm based on ‘‘waterhole behaviour”
– bulk drinking which will only produce mild dehydration and
most probably the positive effects of not only increased oxytocin
but also the second ‘‘thirst” hormone, vasopressin [63]. Although
not mentioned earlier, vasopressin is an important hormone affect-ing human behaviour as evidenced by several investigations show-
ing that vasopressin inﬂuences a wide range of traits, including
increase of social attachment, inhibition of anxiety, improvement
of memory and positive social behaviours [67]. The combined effects of mild increase of oxytocin and vaso-
pressin decreases stress-axis activity, produces a feeling of relax-
ation, increase social bonding, inhibits fear, and regulates
sympathetic/parasympathetic activity [68]. Fear, social isolation,
chronic HPA-axis and sympathetic nervous system activity are
undoubtless related with increased susceptibility for the develop-
ment of inﬂammation and chronic disease [69–71] . Bulk drinking behaviour could therefore recover social beha-
viour, bonding, decrease anxiety, reduce sugar craving, regulate
appetite, induce spontaneous movement, decrease inﬂammation
and inhibit fear. Mild thirst controlled drinking is probably the onlyway to regulate water and mineral homeostasis, whereas the 8 /C28
rule (8 glasses of water of 8 oz each) has not been proven as scien-
tiﬁc sound and protective for health [72]. The effects of bulk drink-
ing as deﬁned in this article are easily testable, measuring different
behavioural traits and several biomarkers. If our hypothesis would
be conﬁrmed we would have ﬁnd one of the cheapest ways to
recover health and collaborative behaviour of people living in a
society characterised by abundance and chronic presence of food
and ﬂuid. Conﬂict of interest
We state that both authors do not have any conﬂict of interest. References
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.L. Pruimboom, D. Reheis / Medical Hypotheses 92 (2016) 80–83 83
Intermittent_Dry_Fasting_lowers_cortisol_by_Pruimboom2016.txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        Intermittent drinking, oxytocin and human health
L. Pruimbooma,b,⇑, D. Reheisa
aNatura Foundation, Edisonstraat 66, 3281 NC Numansdorp, Netherlands
bDepartment of Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen, PO Box 30. 001, 9700 RB Groningen, Netherl ands
article info
Article history:
Received 25 February 2016Revised 26 April 2016Accepted 26 April 2016
Keywords:
Thirst
Addiction
CravingCollaborationHealthEvolutionOxytocinabstract
Looking at a waterhole, it is surprising that so many animals share the same space without visible signs of
anxiety or aggression. Although waterholes are the preferred feeding locations of large carnivores, water-
holes are shared by all type of herbivores of all sizes and shapes, including elephants. Recent researchshows that the homeostatic disturbances leading to the ‘‘thirst feeling” not only activate speciﬁc sub-stances regulating water and mineral household, but also the ‘‘trust and love” hormone oxytocin, while
decreasing the production of the typical stress hormone cortisol. People using drugs, seem to be in search
for oxytocin, as evidenced in studies with individuals on drugs such as ecstasy and gamma-hydroxybyturate. Hot environment, drought and increased sweating also activate speciﬁc oxytocin-
producing parts of the hypothalamus, just as breastfeeding does in mother andinfant. Water homeostasis
is the only allostatic system activating trust neuro-anatomy and we suggest that this is due to the factthat all animals depend on water, whereas food type is species speciﬁc. Our hypothesis; regulating drink-
ing behaviour through intermittent bulk drinking could increase oxytocin signalling, recover human trust
and increase health by down-regulation of stress axis activity and inﬂammatory activity of the immunesystem. Intermittent bulk drinking should be deﬁned as water (including tea and coffee) drinking up to afeeling of satiety and regulated by a mild feeling of thirst. This would mean that people would not drink
less quantity but less frequently and that’s how all animals, but also human newborns behave. It is the
latter group, which is probably the only group of humans with a normal ﬂuid homeostasis. /C2112016 Elsevier Ltd. All rights reserved. 1. Introduction
Stress, broadly deﬁned as a real or perceived threat to home-
ostasis, activates neural circuits that alter the body’s physiology
and behaviour to ensure survival and well-being. Physical stressors
are real threats that create signals within the internal environment
that communicate deviations from homeostasis to the brain. In
contrast, perceived threats or psychogenic stressors create signals
that arise within the brain itself as it interprets stimuli in the exter-
nal environment as potential insults [1]. Both type of stress factors
activate allostatic systems, including the sympathetic nervous sys-tem and hypothalamic circuits, leading to stressful and even
aggressive behaviour [2]. Starvation, infection, dehydration, vio-
lence and climate are ancient stressors producing severe danger
to the body and have therefore shaped ultimate survival function
producing proximate homeostatic feelings to induce behaviour at
service of the ultimate purpose [3]. Perhaps the best example ishumans crying. The ultimate explanation of crying is that it elicits
care and defence from mothers and other care-givers; if infants do
not cry when in need of assistance, it will be less likely to survive. Proximate explanations include both the external triggers of cry-
ing, for example physical separation from the caregiver, cold, or a
lack of food, and also the internal mechanisms, such as the limbic
system and the endogenous opioids involved in the cessation of
crying. These are proximate explanations because they describe
the immediate causal triggers of crying [4]. In this context, the ulti-
mate explanation for hunger is to signal the body for possible star-
vation and death. The proximate value of hunger is that it leads toeating, although eating is also stimulated by looking at, smelling of
and thinking in food, which are therefore all proximate causes of
eating [5]. This so-called thought-shaped fusion can be so strong
that individuals can gain weight just looking at food [6]. Food deﬁ-
ciency as a stress factor activates a complex systemic response,
which should lead to gluconeogenesis, changes in energy distribu-
tion and spontaneous physical activity [7,8]. Starvation may induce
a certain level of aggressive behaviour, which should be considered
adaptive when hunting big game or when suffering from a lack of
high-energy nutrients [9,10], whereas food sharing behaviour is
http://dx. doi. org/10. 1016/j. mehy. 2016. 04. 043
0306-9877/ /C2112016 Elsevier Ltd.
Oxytocin has numerous effects on multiple physiological mechanisms, including influencing the immune system, regulating appetite, and decreasing cortisol production.
What is the purpose of oxytocin in the body?
Humans do not drink in response to thirst and dehydration, but instead drink small amounts frequently, whereas animals drink up to satiety and then stop.
According to the authors, what is the main difference between human drinking behavior and that of animals?
The authors suggest that intermittent drinking (drinking up to satiety and then stopping) could potentially recover human health, trust, and mental well-being by increasing oxytocin signaling and decreasing stress axis activity.
What is the proposed hypothesis in this study?
Oxytocin has anti-inflammatory effects on the immune system and maintains peripheral homeostasis during acute inflammation.
What is the relationship between oxytocin and the immune system?
The authors propose a new drinking rhythm based on the "waterhole" behavior of animals, where one drinks up to satiety and then stops, which could potentially have a positive impact on mental health and well-being.
What is the authors' suggestion for improving human health and mental well-being?