Prolonged Fasting as a Method of Mood Enhancement

in Chronic Pain Syndromes: A Review of Clinical Evidence

and Mechanisms
Andreas Michalsen
Published online: 10 March 2010
# Springer Science+Business Media, LLC 2010
Abstract Periods of deliberate fasting with restriction to
intake of solid food are practiced worldwide, mostly based on
a traditional, cultural, or religious background. Recent
evidence from clinical trials shows that medically supervised
modified fasting (200500 kcal nutritional intake/day) with
periods from 7 to 21 days is efficacious in the treatment of
rheumatic diseases and chronic pain syndromes. Here, fasting
is frequently accompanied by increased alertness and mood
enhancement. The beneficial claims of fasting are supported
by experimental research, which has found fasting to be
associated with increased brain availability of serotonin,
endogenous opioids, and endocannabinoids. Fasting-induced
neuroendocrine activation and mild cellular stress response
with increased production of neurotrophic factors may also
contribute to the mood enhancement of fasting. Fasting
treatments may be useful as an adjunctive therapeutic
approach in chronic pain patients. The mood-enhancing and
pain-relieving effect of therapeutic fasting should be further
evaluated in randomized clinical trials.
Keywords Caloric restriction
.
Diet
.
Fasting
.
Mood
.
Pain
Introduction
A 54-year old woman with chronic low back pain, painful
osteoarthritis of the knee, and metabolic syndrome is
admitted to the Department of Integrative Medicine for
intensified stationary treatment. Besides physical therapies,
she participates in a 7-day modified fasting treatment with a
restricted daily nutritional energy intake of 350 kcal per
day. After 24 h of initial headache due to caffeine withdrawal,
she experiences stable well-being and normalization of
previously increased blood pressure throughout the fasting
period. Contrary to what she expected, she feels not hungry
during the fasting period and experiences increasing pain
relief paralleled by mood enhancement and perceived
increased vitality. After fasting she feels motivated for
continuous lifestyle modification.
This case describes a frequently observed course of
medically supervised modified fasting treatment, which is
established in various specialized departments of Internal
and Integrative Medicine in Western Europe.
The evolution of mankind was, until recent times,
characterized by frequent fluctuations of food availability
varying between periods of fasting or starvation and feast or
overfeeding. The ability to survive periods of fasting must
have been of some survival value and contrasts to the
unfavorable health effects of continuous overfeeding of
present times. Unsurprisingly, therefore, the human body
exhibits adaptive biochemical and physiological responses
to the lack of food. When deprived of food, the human
body employees various behavioral, physiological, and
structural responses to reduce metabolism, which prolongs
the period in which energy reserves can cover metabolism.
On the other hand, after extended fasting periods, physical
activity and psychological performance may increase as
food searching has to be activated [1].
In a cultural context, periods of deliberate fasting with
restriction to intake of solid food have been practiced
worldwide, mostly based on a traditional or religious
background. Still today, fastingthe voluntary abstention
from foodis a common feature of many religions and
A. Michalsen (*)
Immanuel Hospital Berlin,
Department of Internal and Complementary Medicine;
and the Institute of Social Medicine,
Epidemiology and Health Economics,
Charit-University Medical Centre,
Knigstrasse 63,
14109 Berlin, Germany
e-mail: a.michalsen@immanuel.de
Curr Pain Headache Rep (2010) 14:8087
DOI 10.1007/s11916-010-0104-z
ethnic rituals worldwide and is believed to enhance mental
and spiritual alertness [2]. Fasting as a medical treatment is
claimed to be a valuable therapeutic method for chronic and
acute diseases in most of the traditional medical systems
[3, 4]. Here, fasting always is a voluntary act, and the duration
of fasting is limited and predefined. For evaluation of potential
mood-enhancing effects of fasting, the differentiation between
fasting and starvation or hunger is of importance. Thus, results
of studies on starvation, which by definition is involuntary,
only can be translated with some limitations to the condition
of medical fasting. However, experimental research in
animals can only use the model of starvation or controlled
underfeeding, and some uncertainty in the appraisal of these
results with regard to voluntary medical fasting cannot be
resolved.
Different types of fasting have to be differentiated.
Physiologically, nutritional energy supply below a threshold
of about 500 kcal per day leads to strong neuroendocrine
responses of the body and is accompanied by rapid
mobilization of glycogen stores (phase I), followed by
metabolism of fat mass via lipolysis after a fasting duration
more than 24 h (phase II) before the phase of late starvation
with accelerated protein loss (phase III). Whereas the total
withdrawal of calories (total fasting or zero diet) leads to
substantial additional loss of protein mass for gluconeogen-
esis, the daily intake of some calories reduces protein
catabolism by a significant amount [5]. Therefore, clinically,
the daily intake of 200500 kcal by fruits or liquid meals is
established and defines the current mostly used form of
therapeutic fasting, modified fasting. Very low calorie diets
(VLCDs) allow a higher nutritional intake of up to 800 kcal
per day. Yet, whereas VLCD also leads to substantial weight
loss, the adaptive physiological and psychological responses
are reduced compared with total and modified fasting.
Finally, caloric restriction is defined as a long-term reduction
in energy intake without malnutrition, mostly consisting of a
3040% reduction of daily nutritional energy intake [6].
Caloric restriction is commonly used in experimental animal
research. As an alternative to traditional caloric restriction,
another dietary regimen, termed intermittent or alternate day
fasting, has also been established in research. Intermittent
regimens usually involve a feast day on which food is
consumed ad libitum that alternates with a fast day on
which food is withheld [6, 7]. The feast and the fast periods
are typically 24 h. One of the most known religious fasting
traditions is the period of Ramadan. During the fasting
month of Ramadan, Muslims abstain from food and drink
from sunrise until sunset. Thus, Ramadan can be
categorized as a short-period intermittent fasting regimen.
However, in contrast to alternate day fasting, the health-
related effects of the shorter Ramadan fasting periods are
unclear. The main types of fasting are summarized in
Table 1.
There has been much effort in nutritional research in
understanding how the adaption of the human body to food
deprivation is regulated. Despite development in under-
standing of physiological and molecular processes, the
mechanisms associated with the ability of the human body
to cope with extended periods of fasting are still not fully
understood. Clearly, there is a strong link between distinct
neuroendocrine and metabolic adaptive responses and the
psychological effects of fasting. On the other hand, the
clinical pain-relieving and anti-inflammatory effects of
fasting may contribute to mood enhancement and, in turn,
affect neuroendocrine regulation.
In this review, a short historical perspective of fasting is
summarized with clinical data on pain relief and mood
enhancement through fasting, and experimental data and
potential mechanisms are discussed.
Fasting in Medical History
In antique medicine, fasting was an established treatment
method since Hippocrates and thereafter recommended by
most older European medical schools for the treatment of
acute and chronic diseases [2, 8], following the empirical
observation that infections are frequently followed by an
anorectic response [9]. More standardized methods of
extended medical fasting were developed in the United
States in the beginning of the 20th century by Tanner,
Dewey, and Hazzard [4, 10]. Their method of fasting
consisted of water and tea fasting (total fasting), supported
by enemas and physical exercise. Later, some experimental
studies [11] provided a framework for therapeutic fasting
as an accepted inpatient treatment for obesity in the United
States in the 1950s and 1960s. Thereafter, little attention
has been given to the value of medical fasting, and the
method almost disappeared in North America. In contrast,
based on the works of some charismatic physicians,
therapeutic fasting attracted a growing number of patients
from the 1950s on in Europe. The most frequently used
fasting method was created by German physician Otto
Buchinger and was characterized by 13 weeks of modified
fasting, which included the free intake of mineral water and
the limited intake of fruit juice [3, 4]. The fasting cure,
according to the Buchinger technique, is further accompanied
by moderate exercise, nutritional advice, and mind-body
medicine techniques.
Prevalence
In the recent past, modified fasting, according to Buchinger,
and related methods attracted a growing popularity in the
German public as a self-care method for health and
Curr Pain Headache Rep (2010) 14:8087 81
particularly to initiate lifestyle modification [12, 13].
According to a recent survey, personal fasting experience
varied between 15% and 20% in the German population
[14]. In the United States, some 14% of the population
reported using short-term fasting, predominantly to lose
weight [11]. In Europe, fasting treatment is currently
established in more than 20 specialized hospital and
rehabilitation departments [15]. Here, the major treatment
indications are rheumatic diseases, chronic pain syndromes
including chronic headache, and metabolic syndrome.
Clinical Effects of Fasting
The clinical effects of therapeutic fasting have been
investigated by controlled trials in some of the traditionally
claimed indications. The best evaluated indication is
rheumatoid arthritis. Here, four well-designed controlled
trials investigated the effects of fasting with a subsequent
nutritional advice for a follow-up for at least 3 months
[16, 17]. These studies demonstrated a statistically and
clinically significant beneficial long-term effect. A recent
nonrandomized controlled trial also suggested fasting
therapy to be beneficial in the complex treatment of
fibromyalgia [18]. An uncontrolled study from Germany
reported a beneficial effect of headache frequency and
intensity in migraineurs [19]. Furthermore, pain-relieving
and antinociceptive effects of fasting have been described
in some recent experimental studies [20, 21] and confirm
the present data from human studies.
Some studies have further documented a relevant blood
pressurereducing effect of total fasting [22, 23]. The blood
pressurereducing effect of fasting has also led to the
recommendation of fasting experts to reduce medications
with antihypertensive medication when initializing fasting
therapy. Notably, epidemiological studies showed that
routine periodic fasting, as practiced by different religious
groups, is associated with a lower risk of coronary artery
disease in patients undergoing coronary angiography [24].
In a large observational study of inpatients with mixed
diagnosis of chronic diseases, health-related and behavioral
outcomes were compared in fasting patients and patients on
a normocaloric Mediterranean diet [12]. The study was
conducted within an Integrative Medicine hospital in
Germany, where fasting treatment was established in the
disease management pathway and regularly offered to all
patients with suitable indications and without the presence
of predefined exclusion criteria. Fasting patients showed
higher satisfaction ratings with their overall treatment
success and a greater improvement of their main complaint,
which was chronic pain in the majority of patients.
Furthermore, fasting patients showed higher attrition rates
with recommended health-related lifestyle modifications in
the follow-up assessments at 3 and 6 months after discharge
from the hospital. Thus, these results confirmed prior
empirical hypotheses that claimed fasting to act as a reset
for lifestyle modifications [4], as it may interrupt long-term
conditioned health behavior, thereby enhancing more
profound and lasting lifestyle changes.
Mood Enhancement in Chronic Pain Syndromes
In the fasting tradition, it is a common observation that fasting
is accompanied by mood enhancement, improvement of
psychological well-being, and not rarely by a sense of
euphoria [25]. Also, it is a daily life experience that full-
stomach lethargy contrasts with heightened alertness of the
fast. Various authors reported that hunger, during fasting,
returned to baseline levels some days after initiation, thus not
Type of fasting Characteristic Main effect
Modified therapeutic fasting Caloric intake 200500 kcal/
day by fluids
Rapid weight loss; strong
neuroendocrine response
Very low calorie diet Caloric intake 600800 kcal/
day by formulated liquid
meals; protein supplements
Rapid weight loss
Caloric restriction Experimental research; longterm
adaption to undernutrition
Continuous caloric restriction 30%40% daily reduced
caloric intake
Increase of lifespan; reduced
degeneration; improved
functional indexes
Intermittent fasting Alternate-day fasting (24 h) Increase of lifespan; reduced
degeneration; improved
functional indexes
Total fasting 0% caloric intake; water
and tea ad libitum
Rapid weight loss; pronounced
protein catabolism; numerous
adverse effects
Table 1 Principal types of
fasting
82 Curr Pain Headache Rep (2010) 14:8087
affecting mood negatively [11]. Some early observational
and anecdotal reports suggested a specific mood-enhancing
effect of prolonged modified fasting in fasting phase II [2, 3].
A prospective uncontrolled study evaluated physical and
psychological outcomes in 52 patients with metabolic and
chronic pain syndromes undergoing a 2-week modified fast
(250 kcal/day) in a rehabilitation hospital. More than 80%
of fasters showed decreased scores for depression, anxiety,
and exhaustion, accompanied by a mean weight loss of
6.6 kg and a normalization of blood pressure. Psychological
quality of life at the end of the fasting cure was better than
in the general healthy population [26].
In a controlled explorative study, we assessed the effect
of fasting on mood and explored the interaction with
neuroendocrine activation and leptin depletion in patients
with chronic pain syndromes. Of the 55 study subjects, 36
participated in an 8-day modified fast (300 kcal/day), while
19 received a mild low calorie diet. Measurements included
daily ratings of mood (VAS), assessment of weight, and
levels of plasma leptin and cortisol. Weight loss amounted
to 4.8 and 1.6 kg in fasters and controls, respectively. Daily
mood ratings increased highly significantly after 5 fasting
days but were not correlated to weight loss, leptin
depletion, or cortisol increase [27].
In an uncontrolled study with 15 healthy subjects, the
effects of fasting on quality of sleep, polysomnographic
patterns, and subjective well-being were investigated. At
the end of the 8-day fast, subjects experienced an increased
quality of sleep. Emotional well-being in the course of
fasting was characterized by increased daytime concentration,
vigor, and emotional balance. Polysomnography revealed a
significant decrease in arousals and periodic leg movements
and a nonsignificant increase in REM sleep [28]. Thus,
changes in sleep quality and architecture may also influence
fasting-induced mood enhancement.
Further, we assessed perceived daily mood in 108
subjects who underwent an 8-day modified stationary
fasting treatment (350 kcal/day) and analyzed associations
with the genotype. We genotyped for the GNB3 C825T
polymorphism, which is a thrifty genotype associated with
an increased risk for obesity. We observed a genotype-
associated difference in fasting-induced change of mood.
Whereas, TT genotypes experienced an initial decrease and
only moderate late increase of mood, C-allele carriers
showed a significant and consistent fasting-induced mood
enhancement. Moreover, increase in mood was more
pronounced in CC compared with CT genotypes, which is
compatible with a gene-dose effect [29].
In summary, preliminary evidence from uncontrolled and
controlled trials confirms the empirical observation that
fasting may be associated with mood enhancement, which
seems to be more pronounced in the late phase of fasting,
emerging after 45 fasting days. Of note, all mentioned
studies found that modified fasting was safe and not
associated with relevant feelings of hunger. Further and
larger controlled clinical trials are needed to verify this
preliminary evidence. Such studies should also compare the
effects of modified fasting with other forms of caloric
restriction in order to better understand the underlying
mechanisms.
Mechanisms of Fasting-induced Mood Enhancement
Physiological and Endocrine Responses to Extended
Fasting
Extended fasting represents a strong physiological stimulus
and induces pronounced hormonal changes (eg, stimulation
of the hypothalamic-pituitary-adrenal axis as the characteristic
physiologic equivalent of a stress reaction) [3032]. It is not
clear which factors initiate this neuroendocrine activation,
but decreased brain glucose availability, leptin and insulin
depletion, and perceived hunger may play a prominent role
[5, 33, 34]. Recently, a transcription factor has been
described, which acts as a metabolic sensor in neurons of
the lateral hypothalamic area to integrate metabolic signals,
adaptive behavior, and physiological responses [35].
In human clinical studies, the fasting-induced neuroendo-
crine activation is associated with increased urinary and serum
concentrations of noradrenaline, adrenaline, dopamine, and
cortisol. This early hypopituitary-adrenergic activation is
followed by decreased adrenergic levels in the midterm. In a
prospective study with obese subjects, fasting over 16 days
led to substantial weight loss paralleled by decreased basal
and exercise-induced serum concentrations of noradrenaline,
adrenaline, and dopamine [36]. Moreover, extended periods
of fasting are associated with increases of concentrations of
the growth hormone glucagon and reductions of the blood
levels of thyrotropin and T
3
/T
4
[31]. Clinically, fasting is
further associated with a pronounced initial natriuresis and
diuresis. The mechanisms of the natriuresis of fasting remain
partly unclear; however, ketoacidosis and fasting-induced
increases of blood levels of aldosterone, glucagon, and
natriuretic peptides are involved [37]. Studies on VLCD
demonstrated an increased blood pressurelowering effect of
natriuretic peptides after a 4-day diet period, which may
point to increases in receptor sensitivity following periods of
fasting or underfeeding [38]. Accordingly, blood levels of
insulin are decreased after fasting periods with subsequently
increased insulin receptor sensitivity.
We and others have shown that fasting leads to rapid
depletion of the adipokine leptin and reductions of blood
levels of insulin [27, 33, 39]. Low levels of leptin
indicating food deprivation have been identified as strong
signals to induce adaptive biological actions; thus, leptin
Curr Pain Headache Rep (2010) 14:8087 83
depletion may play a crucial role in the neuroendocrine
signalling in response to fasting [40]. There is also increasing
evidence that leptin is implicated in mood disorders [41], and
leptin modulates putative brain reward circuitry by enhanc-
ing the value of behaviors incompatible with feeding [42]. In
concert with other signals from the gut, low leptin levels can
trigger powerful activation of brain systems to restore energy
balance. The most relevant neuroendocrine changes during
extended fasting are summarized in Table 2.
Neurobiological Effects of Extended and Intermittent
Fasting
Brain neurotransmitters may also be implicated in the
fasting-induced modification of mood. The central seroto-
nergic system is strongly involved in the regulation of food
intake, and it is also a transmitter system that is readily
affected by nutritional factors.
Serotonin release and turnover are known to increase
during extended fasting [43, 44]. Increased output of the
serotonergic system is thought to be responsible for some of
the characteristic nutritional effects on certain brain functions
such as elevated mood, increased sleepiness, and reduced
pain sensitivity. Fasting is associated with increases in
tryptophan availability and serotonin turnover in the brain.
Recent research indicated that semistarvation is associated
with downregulation of cortical serotonin transporters in the
frontal cortex of the rat, and alteration of the serotonin output
pattern may also affect projection fields of the central
serotonergic system [45]. Thus, fasting-induced modulation
of central serotonin availability may be a potential mecha-
nism and would also explain previously described effects of
fasting treatments in migraineurs [19], as pharmacological 5
HT-receptor inhibition has been proven effective in the
treatment of migraine. Furthermore, brain-derived neuro-
trophic factors (BDNFs), which are induced by intermittent
fasting, may be implicated in central serotonergic regulation
[46]. Recent research indicates a reciprocal relationship
between BDNF and serotonergic signaling, in which BDNF
enhances serotonin production and release [47, 48].
Another potential mechanism of mood enhancement
relates to fasting-induced alteration of endogenous opioid
release. Plasma -endorphin levels in subjects undergoing
fasting periods between 5 to 10 days were significantly
increased during the fasting time, while there was no direct
association with body weight changes [49]. Also, differential
regulation of the endogenous synthetic pathways of
morphine in response to fasting has been described.
Brain morphine levels were elevated fivefold after 24 h
of fasting and twofold after 48 h of fasting in rats
[50]. Moreover, brain levels of the endogenous cannabinoid
2-arachidonoyl glycerol were found to be increased in fasting
mice, while diet restriction had no influence [51].
Recent research in molecular biology of caloric restriction
has revealed further potential mechanisms that may also
contribute to the mood-enhancing and pain-relieving effects
of fasting. It is a well-known fact that caloric restriction
increases the maximum lifespan in all examined animal
species [52]. It was recently shown that caloric restriction
and intermittent fasting not only reduced the risk of
different age-related diseases, including cardiovascular
disease, diabetes, and cancers, but also of most neurode-
generative disorders (eg, Parkinsons and Alzheimers
disease) [46, 53].
These beneficial neurological effects of fasting may be
linked to the elicitation of a cellular stress response due to
decreased glucose availability to the brain cells. Neurons
respond to the cellular stress response by activating signaling
pathways that induce the expression of genes encoding
proteins that promote neuronal survival and plasticity [46].
In fact, fasting can stimulate the production of new neurons
from stem cells (neurogenesis) and can enhance synaptic
plasticity, which modulate pain sensation, enhance cognitive
function, and may increase the ability of the brain to resist
aging [54]. The beneficial effects of fasting seem to be
related to the stimulated production of proteins that include
neurotrophic factors, neurotransmitter receptors, and protein
chaperones [55].
For example, fasting increases the production of BDNF
in different regions of the brain. BDNF can enhance
learning and memory, protect neurons against oxidative
and metabolic insults, and stimulate neurogenesis [46, 53];
these actions may protect neurons against age-related
neurodegenerative disorders but may also contribute to
mood enhancement in humans. Other neuropeptides linked
to the regulation of eating behavior, appetite, and mood are
orexins and neuropeptide Y. These neuropeptides are
Table 2 Neuroendocrine responses of fasting
Variable Early fasting phase
a
Late fasting phase
a
Adrenaline
Noradrenaline
Cortisol
Natriuretic peptide
Leptin
Insulin
Adiponectin
Serotonin
Growth hormone
Glucagon
T3 T4
Neurotrophic factors
a
Early phase of fasting may vary between 2 and 7 days; late phase of
fasting between day 8 and 20.
84 Curr Pain Headache Rep (2010) 14:8087
inhibited in response to feeding-related signals and are
released during fasting. In rodents, fasting increases
expression of the neuropeptide Y gene in defined brain
regions. Neuropeptide Yacts via its spinal receptors to reduce
spinal neuron activity and behavioral signs of inflammatory
and neuropathic pain [56]. Thus, a pain-relieving effect of
fasting-induced neuropeptide Y seems likely. A decrease in
orexin levels has been reported to be associated with
depression. It was also shown that stress and depression
can disrupt neurogenesis in the hippocampus. Here, results
from experimental studies suggest that orexins induce an
antidepressive-like effect via the enhancement of cell
proliferation in the hippocampus [57].
In summary, fasting may activate specific self-protective
cellular stress resistance mechanisms overriding any poten-
tially deleterious effects of elevated glucocorticoids and
catecholamines. In contrast, overfeeding, which is associated
with chronic neuroendocrine activation, promotes neuronal
degeneration and impairs neurogenesis.
Finally, the fasting-induced increase in production of
ketone bodies may contribute to psychological and pain-
relieving effects. It is well known that ketone bodies may
protect neurons against multiple types of neuronal injury
and hypoglycemia, and the underlying mechanisms are
similar to those of calorie restriction [54]. Anticonvulsant
effects have been repeatedly demonstrated. However, so far
it remains unclear if ketone bodies are involved in the
neurobiological effects of fasting.
The most relevant mechanisms and neurobiological
interactions regulating mood and pain perception during
fasting are summarized in Fig. 1.
Reflecting on the given findings, mood enhancement
during fasting may represent a phylogenetically useful
mechanism promoting success in the fight for survival
and the search for food. Presumably, it must have been an
evolutionary advantage and increased the ability of our
ancestors to cope with phases of restricted access to food,
that mood enhancement followed limited periods of fasting.
Mood enhancement, together with increased alertness and
motor activity, thus probably reduced the susceptibility to
detrimental influences of psychological distress due to
underfeeding.
Of note, the motivation to engage in periodical fasting in
the religious context seems to be driven by a deliberate
renunciation of exogenous gratifications on the background
of asceticism. However, the current widespread practice of
periodical fasting worldwide may also be supported by the
concomitant increase of alertness, tranquillity, and mood
enhancement [58].
Practical Aspects of Clinical Fasting
Fasting is an established treatment method within specialized
hospitals or hospital departments of Integrative and Nutri-
tional Medicine in various central European countries. Within
expert conferences, quality criteria of medical fasting have
been defined [59]. A fasting period between 1 and 2 weeks is
generally recommended to induce clinically relevant effects
in chronic pain patients. Furthermore, exclusion criteria to
fasting were defined and should be strictly considered in the
practice of fasting treatments.
Most relevant contraindications are eating disorders, a
body mass index of less than 20 kg/m
2
or greater than
40 kg/m
2
, liver disease, renal failure, gastric ulcer, and
other severe comorbidities, including cancer, premedication
with immunosuppressive drugs (except corticosteroids) or
coumarins, alcoholism, psychosis, pregnancy, lactation, and
unexplained weight loss.
An optimum fasting regimen is preceded by two relief
or prefasting days, using a 800 kcal/day monodiet of fruit,
rice, or potatoes according to patients choice. Fasting then
Fig. 1 Mechanisms and interac-
tions regulating mood and pain
perception during fasting
Curr Pain Headache Rep (2010) 14:8087 85
starts with ingestion of a mild oral laxative. During fasting,
patients are recommended to drink 2 to 3 liters of fluids
each day (mineral water, small quantities of juice, and
herbal teas). The daily energy intake should amount
between 200 to 500 kcal. The break-fast is followed by
stepwise reintroduction of food with achievement of normo-
caloric intake by vegetarian meals on the fourth postfast day.
In the postfasting days, a focus is set on reintroducing
mindfulness to eating.
With this concept, therapeutic modified fasting has been
found to be a safe treatment method. Rare adverse effects
include tiredness, irritability, headache, nausea, lightheaded-
ness, and gastric pain. To avoid any hyponatremia, fasting is
not allowed in the presence of diuretic medication. Dosages of
coumarins have to be closely monitored during fasting, as the
fasting-associated interruption of oral vitamin K intake
reduces necessary dosage.
The described fasting method has a very high adherence
rate in patients with chronic pain syndromes and rheumatic
disease. In our experience, such periods of extended fasting
seem to be much easier to apply in patients than intermittent
fasting diets, in which hunger is a frequent discomfort during
the restriction days. Furthermore, concerning feasibility,
extended fasting periods seem to compare better to chronic
caloric restriction, which is hard to sustain in daily life.
Conclusions
In chronic pain patients, medically supervised fasting over
periods of 720 days is associated with mood enhancement
and substantial pain relief. The current preliminary evidence
suggests that fasting treatment could be useful as an
adjunctive therapeutic approach in chronic pain patients,
which are most frequently affected by depression and anxiety.
The mood-enhancing and potential antidepressive effects of
fasting in patients with or without chronic pain syndromes
should be further evaluated in larger controlled clinical trials.
Disclosure No potential conflicts of interest relevant to this article
were reported.
References
Papers of particular interest, published recently, have been
highlighted as:
Of importance
Of major importance
1. Wang T, Hung CC, Randall DJ: The comparative physiology of
food deprivation: from feast to famine. Annu Rev Physiol 2006,
68:223251.
2. Ltzner H: Fasten. Bindlach: Gondrom Verlag; 2002.
3. Fahrner H: Fasten als Therapie. Stuttgart: Hippokrates; 1991.
4. Buchinger A: Fasting. In Clinicians Complete Reference to
Complementary and Alternative Medicine. Edited by Nowey
DW. St. Louis: Mosby; 2000.
5. Owen OE, Smalley KJ, DAlessio DA, et al.: Protein, fat, and
carbohydrate requirements during starvation: anaplerosis and
cataplerosis. Am J Clin Nutr 1998, 68:1234.
6. Varady KA, Hellerstein MK: Alternate-day fasting and chronic
disease prevention: a review of human and animal trials. Am J
Clin Nutr 2007, 86:713.
7. Varady KA, Bhutani S, Church EC, Klempel MC: Short-term
modified alternate-day fasting: a novel dietary strategy for
weight loss and cardioprotection in obese adults. Am J Clin
Nutr 2009, 90:11381143. This review summarizes metabolic
and cardioprotective effects of calorie restriction.
8. Ltzner H: Fasten/Fastentherapie. In Naturheilverfahren und
Unkonventionelle Medizinische Richtungen. Edited by Bhring
M, Kemper FH. Berlin: Springer; 1998:126.
9. Exton MS: Infection-induced anorexia: active host defence
strategy. Appetite 1997, 29:369383.
10. Shelton H: The Hygienic System. Fasting and Sun Bathing. San
Antonio, TX: Dr. Sheltons Health School; 1963.
11. Johnstone AM: Fasting: the ultimate diet? Obes Rev 2007, 8:211
222. This review gives an overview of clinical and physiological
effects of fasting used for weight loss in obese patients.
12. Michalsen A, Hoffmann B, Moebus S, et al.: Incorporation of
fasting therapy in an integrative medicine ward: evaluation of
outcome, safety, and effects on lifestyle adherence in a large
prospective cohort study. J Altern Complement Med 2005,
11:601607. (Published erratum appears in J Altern Complement
Med 2005, 11:1121.)
13. Hartel U, Volger E: Inanspruchnahme und Akzeptanz klassischer
Naturheilverfahren und alternativer Heilmethoden in Deutschland
Ergebnisse einer reprasentativen Bevolkerungsstudie. Forsch
Komplementarmed Klass Naturheilkd 2004, 11:327334.
14. Stange R, Amhof R, Moebus S: Complementary and alternative
medicine: attitudes and patterns of use by German physicians in
a national survey. J Altern Complement Med 2008, 14:1255
1261.
15. Wilhelmi de Toledo F: Fasten/Fastentherapie: physiologie des
fastens. In Fasten/Fastentherapie: Physiologie des Fastens. Edited
by Springer LoseblattSammlung. Berlin; 1998.
16. Mller H, de Toledo FW, Resch KL: Fasting followed by
vegetarian diet in patients with rheumatoid arthritis: a systematic
review. Scand J Rheumatol 2000, 30:110.
17. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, et al.: Controlled
trial of fasting and one-year vegetarian diet in rheumatoid arthritis.
Lancet 1991, 338:899902.
18. Michalsen A, Riegert M, Ldtke R, et al.: Mediterranean diet or
extended fastings influence on changing the intestinal microflora,
immunoglobulin A secretion and clinical outcome in patients with
rheumatoid arthritis and fibromyalgia: an observational study.
BMC Complement Altern Med 2005, 5:22.
19. Lipecki R: Klinische Studie zur Effizienz einer kombinierten
Heilfastenbehandlung als Migrnetherapie. Inaugural Dissertation
1990, Universitt Wrzburg:153.
20. Hargraves WA, Hentall ID: Analgesic effects of dietary caloric
restriction in adult mice. Pain 2005, 114:455461.
21. de los Santos-Arteaga M, Sierra-Dominguez SA, Fontanella
GH, et al.: Analgesia induced by dietary restriction is mediated
by the kappa-opioid system. J Neurosci 2003, 23:11120
11126.
22. Mller H, Wilhelmi de Toledo F, Schuck P, Resch KL.
Blutdrucksenkung durch Fasten bei adipsen und nichtadipsen
Hypertonikern. Perfusion 2001, 14:108112.
86 Curr Pain Headache Rep (2010) 14:8087
23. Goldhamer AC, Lisle DJ, Sultana P, et al.: Medically supervised
water-only fasting in the treatment of borderline hypertension. J
Altern Complement Med 2002, 8:643650.
24. Horne BD, May HT, Anderson JL, et al.: Usefulness of routine
periodic fasting to lower risk of coronary artery disease in patients
undergoing coronary angiography. Am J Cardiol 2008, 102:814
819.
25. Michalsen A, Weidenhammer W, Melchart D, et al. Short-term
therapeutic fasting in the treatment of chronic pain and fatigue
syndromes: well-being and side effects with and without mineral
supplements [in German]. Forsch Komplementarmed Klass
Naturheilkd 2002, 9:221227.
26. Peper E, Rogner J, Hettwer H: Stationres Heilfasten. Pr-/Post-
Befragung zum krperlichen und emotionalen Befinden sowie
erlebten Vernderungen. Prv.-Rehab 1996, 8:129136.
27. Michalsen A, Kuhlmann MK, Ldtke R, et al.: Prolonged
fasting in patients with chronic pain syndromes leads to late
mood-enhancement not related to weight loss and fasting-induced
leptin depletion. Nutr Neurosci 2006, 9:195200. This report
describes the mood-enhancing effect of extended fasting as
observed in a controlled study in patients with chronic pain
syndromes.
28. Michalsen A, Schlegel F, Rodenbeck A, et al.: Effects of short-term
modified fasting on sleep patterns and daytime vigilance in non-
obese subjects: results of a pilot study. Ann Nutr Metab 2003,
47:194200.
29. Michalsen A, Frey UH, Merse S, et al.: Hunger and mood during
extended fasting are dependent on the GNB3 C825T polymorphism.
Ann Nutr Metab 2009, 54:184188.
30. Schwartz MW, Seeley RJ: Seminars in medicine of the Beth Israel
Deaconess Medical Center. Neuroendocrine responses to starvation
and weight loss. N Engl J Med 1997, 336:18021811.
31. Palmblad J, Levi L, Burger A, et al.: Effects of total energy
withdrawal (fasting) on the levels of growth hormone, thyrotropin,
cortisol, adrenaline, noradrenaline, T4, T3 and rT3 in healthy
males. Acta Med Scand 1977, 201:1522.
32. Michalsen A, Schneider S, Rodenbeck A, et al.: The short-term
effects of fasting on the neuroendocrine system in patients with
chronic pain syndromes. Nutr Neurosci 2003, 6:1118.
33. Bergendahl M, Evans WS, Pastor C, et al.: Short-term fasting
suppresses leptin and (conversely) activates disorderly growth
hormone secretion in midluteal phase women: a clinical research
center study. J Clin Endocrinol Metab 1999, 84:883894.
34. Ahima RS, Prabakaran D, Mantzoros C, et al.: Role of leptin in
the neuroendocrine response to fasting. Nature 1996, 382:250
252.
35. Silva JP, von Meyenn F, Howell J, et al.: Regulation of adaptive
behavior during fasting by hypothalamic Foxa2. Nature 2009,
462:646650.
36. Ghler L, Hahnemann T, Michael N, et al.: Reduction of plasma
catecholamines in humans during clinically controlled severe
underfeeding. Prev Med 2000, 30:95102.
37. Spark RF, Arky RA, Boulter PR, et al.: Renin, aldosterone and
glucagon in the natriuresis of fasting. N Engl J Med 1975,
292:13351340.
38. Maoz E, Shamiss A, Peleg E, et al.: The role of atrial natriuretic
peptide in natriuresis of fasting. J Hypertens 1992, 10:10411044.
39. Horowitz JF, Coppack SW, Paramore D, et al.: Effects of short-term
fasting on lipid kinetics in lean and obese woman. Am J Physiol
1999, 276:E278E284.
40. Ahima RS, Lazar MA: Adipokines and the peripheral and neural
control of energy balance. Mol Endocrinol 2008, 22:10231031.
This report describes the role of leptin and adipokines in the
regulation of nutritional energy balance.
41. Tichomirowa MA, Keck ME, Schneider HJ, et al.: Endocrine
disturbances in depression. J Endocrinol Invest 2005, 28:8999.
42. Fulton S, Woodside B, Shizgal P: Modulation of brain reward
circuitry by leptin. Science 2000, 287:125128. (Published
erratum appears in Science 2000, 287:1931.)
43. Schweiger U, Broocks A, Tuschl RJ, Pirke KM: Serotonin
turnover in rat brain during semistarvation with high-protein and
high-carbohydrate diets. J Neural Transm 1989, 77:131139.
44. Curzon G, Joseph MH, Knott PJ: Effects of immobilization and food
deprivation on rat brain tryptophan metabolism. J Neurochem 1972,
19:19671974.
45. Huether G, Zhou D, Schmidt S, et al.: Long-term food restriction
down-regulates the density of serotonin transporters in the rat
frontal cortex. Biol Psychiatry 1997, 41:11741180.
46. Mattson MP: Energy intake, meal frequency, and health: a
neurobiological perspective. Annu Rev Nutr 2005, 25:237260.
47. Goggi J, Pullar IA, Carney SL, Bradford HF: Modulation of
neurotransmitter release induced by brain-derived neurotrophic
factor in rat brain striatal slices in vitro. Brain Res 2002, 941:34
42.
48. Rumajogee P, Madeira A, Verg D, et al.: Up-regulation of the
neuronal serotoninergic phenotype in vitro: BDNF and cAMP
share Trk B-dependent mechanisms. J Neurochem 2002,
83:15251528.
49. Komaki G, Tamai H, Sumioki H, et al.: Plasma beta-endorphin
during fasting in man. Horm Res 1990, 33:239243.
50. Molina PE, Hashiguchi Y, Meijerink WJ, et al.: Modulation of
endogenous opiate production: effect of fasting. Biochem Biophys
Res Commun 1995, 207:312317.
51. Hanus L, Avraham Y, Ben-Shushan D, et al.: Short-term fasting
and prolonged semistarvation have opposite effects on 2-AG
levels in mouse brain. Brain Res 2003, 983:144151.
52. Mattson MP, Wan R: Beneficial effects of intermittent fasting and
caloric restriction on the cardiovascular and cerebrovascular
systems. J Nutr Biochem 2005, 16:129137.
53. Mattson MP, Chan SL, Duan W: Modification of brain aging and
neurodegenerative disorders by genes, diet, and behavior. Physiol
Rev 2002, 82:637672.
54. Maalouf MA, Rho JM, Mattson MP: The neuroprotective
properties of calorie restriction, the ketogenic diet, and ketone
bodies. Brain Res Rev 2009, 59:293315. This review gives an
overview of the potential neuroprotective effects of calorie
restriction, fasting, and ketone bodies.
55. Fontn-Lozano A, Lpez-Lluch G, Delgado-Garca JM, et al.:
Molecular bases of caloric restriction regulation of neuronal
synaptic plasticity. Mol Neurobiol 2008, 38:167177. This review
discusses the effects of fasting and calorie restriction on brain
function and cellular/synaptic processes underlying analgesia and
cognitive function.
56. Taylor BK, Abhyankar SS, Vo NT, et al.: Neuropeptide Yacts at
Y1 receptors in the rostral ventral medulla to inhibit neuropathic
pain. Pain 2007, 131:8395. This report illustrates how neuro-
peptide Y, which is also modified by fasting, is involved in the
spinal transmission of pain.
57. Ito N, Yabe T, Gamo Y, et al.: I.c.v. administration of orexin-A
induces an antidepressive-like effect through hippocampal cell
proliferation. Neuroscience 2008, 157:720732.
58. Mehta LH, Roth GS: Caloric restriction and longevity: the
science and the ascetic experience. Ann N Y Acad Sci 2009,
1172:2833. This review discusses the ascetic background of
fasting tradition and implications for current research on the
effects of caloric restriction.
59. Wilhelmi de Toledo F, Buchinger A, Burggrabe H, et al.: Guidelines
of fasting therapy. Forsch Komplementarmed 2002, 189199.
Curr Pain Headache Rep (2010) 14:8087 87