Islamic fasting and Multiple Sclerosis
Soodeh Razeghi Jahromi1, Mohammad Ali Sahraian1 , Fereshteh Ashtari2, Hormoz Ayramloo3, Massoud
Etemadifar2, Majid Ghaffarpour4, Ehsan Mohammadiannejad5, Shahryar Nafissi6, Alireza Nickseresht7, Vahid
Shayegannejad8, Mansoreh Togha1 , Hamid Reza Torabi9, Shadi Ziaie10
1.
MS Research Center- Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences.
2.
Department of Neurology, Azahra Hospital, Esfahan University of Medical Sciences.
3.
Department of Neurology, Faculty of Medicine, Tabriz University of Medical Sciences.
4.
Iranian Center for Neurological Research, Imam Khomini Hospital, Tehran University of Medical
Sciences.
5.
Department of Neurology, Golestan Hospital, Ahwaz University of Medical Sciences.
6.
Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences.
7.
Department of Neurology, Namazi Hospital, Shiraz University of Medical Sciences.
8.
Department of Neurology, Kashani Hospital, Esfahan University of Medical Sciences
9.
Jam Hospital, Iranian MS Society
10. Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of medical Sciences
Corresponding author:
Mohammad Ali Sahraian, MD
MS Research Center, Neuroscience Institute, Sina Hospital, Hasan abad Square, Tehran-Iran
Tel: +98 21 66348571
Fax: +98 21 66348570
Email: msahrai@sina.tums.ac.ir
1
Abstract
Background: The month-long daytime Ramadan fasting pose a major challenge to multiple sclerosis (MS) patients
in Muslim countries. Physician should have practical knowledge on the implications of fasting on MS. In this article,
we present a summary of a symposium on Ramadan fasting and MS. In this symposium, we aimed to review the
effect of fasting on MS and suggest practical management guides.
Discussion: Generally, fasting is possible for most stable patients. Proper amendment of drug regimen, careful
monitoring of clinical symptoms, as well as providing patients with available evidences on fasting and MS are
important parts of clinical management. Current evidences from experimental studies suggest that calorie restriction
prior to disease induction reduces inflammation and subsequent demylination and as a result attenuates disease
severity. A recent study examining the effect of fasting on MS showed that fasting had no unfavorable effect on the
course of disease in patients with mild disability (disability status scale ≤3). More studies are needed to assess the
effects of symptomatic treatment and the duration of fasting on MS. However, a majority of experts believed that
during fasting especially in summer, some of MS symptoms including fatigue, fatigue perception, dizziness,
spasticity, cognitive problems, weakness, vision, balance, and gait might worsen; but usually return to normal level
during feast time. There was also a general consensus that fasting is not safe for patients on high dose of
anticonvulsants, antispastics, and corticosteroids, patients with coagulopathy or active disease, during attacks and in
patients with disability status scale ≥7.
Summary: MS patients should be managed individually. Indeed, fasting in MS patients is a challenge that is
directly associated with the patients’ will.
Keywords: Ramadan fasting, multiple sclerosis, calorie restriction
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Introduction
Several religions recommend times of fasting. A 2009-demographic study reported that 23% (1.57 billion) of the
world’s population are Muslims [1]. This percent is growing by 3% per year. Ramadan fasting is considered as one
of the five pillars of Islam and day-time fasting during the holy month of Ramadan is obligatory for all healthy
adults. Muslims are forbidden from eating, drinking, smoking, and sexual relationship from husk to down. Travelers,
menstruating, pregnant, and lactating women, children, particular sick persons and debilitates are exempt from
fasting [2]. However, many Muslims who are eligible for exemption including individuals with mild, moderate, and
severe medical conditions choose to fast. More ever, recent evidences revealed that there is no contraindication to
Islamic fasting for patients with mild coronary artery disease, valvular problems, stable asthma, many of the type-2
diabetes, asympthomatic peptic ulcer, and intestinal motility disorders. Consequently, the Muslim patients are
seeking advice about the safety and feasibility of fasting[3]
Multiple sclerosis (MS) is one of these medical conditions. MS is a chronic demyelinating disease with an unclear
etiology that affect approximately two-and-a-half million individuals worldwide and identified as the most common
debilitating neurological disease in young adults[4]. MS is an immune-mediated inflammatory disease of the central
nervous system (CNS) that, in the most severe cases, can lead to irreversible clinical disability[5]. The concern for
Muslim MS patients is weather Ramadan fasting might have an unfavorable effect on disease course. This debate
became more challenging after the work of Esquifino et al. on the animal model of MS, known as Experimental
Autoimmune Encephalomyelitis (EAE). In human and animal studies, the effect of fasting on health is commonly
studied in three forms: calorie restriction (CR), alternate-day fasting (ADF) and dietary restriction. ADF and CR
may induce similar metabolic and physiological changes. Esquifino et al. reported that Calorie Restriction (CR)
improves signs of EAE[6]. Hence, we aimed to review the opinions of neurologist involving in management of
patients with MS, about the medical impact of Ramadan fasting on this disease, irrespective of their religious
believes.
For this purpose we firstly reviewed the current evidences about fasting and multiple sclerosis. Secondly, we
presented a coincise summary of the points discussed in the mini-symposium on the effect of fasting on MS patients.
In the mentioned symposium we asked the neurologists, nutritionists, and clinical pharmacists to present a summary
of available evidences, as well as their clinical experiences about fasting and MS. Consequently we aimed to provide
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practical guidance for MS patients who decided to fast with respect to their general health, disability score, level of
activity, sex, weight, symptoms and job.
Discussion
Information has been sought through the Cochrane and PubMed data bases. All relevant abstracted reports have
been considered from the initiation of these data bases to June 2013, combining the term “Ramadan” (476 entries)
with terms specific to each of the topics under investigation. Also all relevant abstract about “ketogenic diet” (703
items), as well as about“calorie restriction” or “fasting” combined with the terms “neuroprotection” and”
immunity” (38 items) were reviewed.
Fasting in animal studies
CR with nutritional maintenance has been proposed to extend life span in the following species: fruit fly, nematode,
zebra fish, spider, rodent, and rotifer [7]. In addition to slowing the aging process, CR has been demonstrated to
delay the onset of several diseases including: atherosclerosis, cardiomyopathies, renal disease, diabetes, cancers, and
respiratory disease [7].
Among neurological disease, fasting and more generally CR represents the first effective treatment for epilepsy in
medical history [8]. CR results in an increase in serum level of the ketone body, Beta-hydroxybutyrate. This rise in
beta-hydroxybutyrate level correlates with a significant reduction in the vulnerability of hippocampal neurons to
kainite injection. In 1920s, the ketogenic characteristics of calorie restriction lead to development of high-fat, lowcarbohydrate ketogenic diet [8]. Antiepileptic properties of KD could be explained in part with its ant-apoptotic and
anti-oxidative properties. Recent studies suggested that nuclear clusterin, a proapoptotic protein, did not accumulate
in the hippocampus of KD-fed mice induced with kainic acid (KA) [9]. KD also reduced the KA-induced cell death
in the hippocampus by reducing caspase-3 level and blocking the dissociation of Bad from 14-3-3 proteins [10]. Noh
et al. performed an in-vitro study on the effect of acetoacetate (AA) on glutamate cytotoxicity in a rat primary
hippocampal neurons and mouse hippocampus cell line (HT22). Pretreatment with AA reduced reactive oxygen
species (ROS) production of HT22 cell line. AA also decreased the appearance of popidium iodine-positive and
annexin V-positive HT22 cells which are representative of necrosis and apoptosis [11].
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Accumulating data suggested that the beneficial effects of CR were not limited to ketogenic properties. Calorie
restriction per se have profound neuroprotective effects in animal models relevant to the pathogenesis of
neurodegenerative disorders like Huntington's, Parkinson's, Alzheimer's and stroke. Opalach K et al. investigated the
effect of 40% life-long calorie restriction on age-related oxidative damages of peripheral nerves. They found that
CR ameliorates the age-related accumulation of cross-linked and oxidized substances in the peripheral nerves. CR
also attenuated age-related nuclear factor kB (NFkB), phospho-IkB, and tumor necrotizing factor α (TNF-α)
increments [12]. Age-related oxidation of myelin polyunsaturated fatty acids results in the formation of
hydroxyalkenals and hydroperoxidase, like 4-hydroxynonenal (HNE) and malondialdehyde (MDA) which reacts
with proteins and change their surface hydrophobicity. CR suppressed age-related increase in MDA-adducted
proteins of siatic nerves. CR also reduced HNE-positive area throughout axonal and glial compartments [12].
Several other molecular and cellular mechanisms were also proposed for the neuroprotective action of CR including:
decrease mitochondrial production of free radicals [13], the promotion of antioxidant defense [8], induction of
bioenergetics [8, 14], elevation of sirtuin activity [15], rise in neurotrophic factors activity [8], increase of protein
chaperone activity [8], enhancement of neurogenesis [8], imposing anti-inflammatory properties, [8] , reduction of
leptin level [16], and reduction of oligodendrocyte apoptosis [7]. Each of which, make CR beneficial in protecting
against MS and EAE.
Up to the best of our knowledge, there are only three studies on CR in animal model of MS-experimental
autoimmune encephalomyelitis (EAE). In two of these, Esquifino et al. found that restricting energy intake by 33%
or 66% from 15 days prior to EAE induction, would decrease the severity of disease in rats [17-18]. Rats in the later
group were totally protected against EAE. Subjecting to 66% CR led to impaired lymphocyte proliferation,
decreased CD4+ cells in lymphoid organs, and suppressed Interferon gamma (IFN-γ) production.
In Piccio et al. study, mice were subjected to 40% calorie restriction from five weeks prior to disease induction.
They observed comparable beneficial effect on the course of disease[19]. In the mentioned study CR worked
through the enhancement of endogenous glucocorticoid production, but not through immune system suppression.
In above three mentioned studies, the following mechanisms have been proposed for the beneficial effects of CR:
Concept 1: Improving the function of immune system
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Long-term calorie restriction improves T-cell function and delays immune senescence. According to Squifino et al.
study, 66% CR resulted in modification of 24-hour rhytmicity of T-B lymph nodes, T lymphocytes, CD4+-CD8+
and CD4+ cells subsets function, as well as, lymph node mitogenic responses to Concanavalin A and
lipopolysaccaride. Furthermore, mean values of Submaximally lymph node Con A response and CD4+ cell number
increased. On the other hand, the number of B-cells and the secretion of IFN-γ decreased[20]. In Piccio et al. study,
40% calorie restriction ameliorated EAE signs, without suppression of T-cell proliferation. Long term CR reduced
susceptibility to infectious disease by enhancing T-cell function [19]. Collectively, applying calorie restriction prior
to disease induction, protect against EAE, by improving T-cell function.
Concept 2: CR enhances glucocorticoids production
Glucocorticoids have inhibitory effects on inflammatory gene expression [21]. Systemic corticosteroid
administration is known as standard treatment in MS exacerbation [22]. In rodent, treatment with exogenous
glucocorticoids blocks EAE[23]. In Piccio et al. study, four weeks CR increased corticosterone level[19].
Interestingly, endogenous production of corticosterone would avoid side-effects reported in exogenous
administration of steroids[19].
Concept 3: imposing immunomodulatory effect
Interleukin 6 (IL-6) can be produced by adipose tissue. Four weeks of CR reduced body fat and consequently, IL-6
level. IL-6 has critical role in EAE induction. EAE cannot be induced IL-6 in mice [19]. IL-6 together with
Transforming growth factor beta (TGF-β), has been reported to inhibit the production of T regulatory cells, results in
suppression of T-helper 17 (Th-17) gene expression [19]. Expression of Th-17 known as one of the main features of
MS [24].
Fasting in human studies
There are limited evidences about fasting, especially Islamic fasting and MS. However, the immunomodulatory and
anti-oxidative properties of fasting have recently been the subjects of scientific investigations.
Effects of fasting on immune system in human beings
6
Ahmed T et al. performed a study on 6-weeks 30% or 10% CR in 40 healthy overweight men and women. They
reported that delayed-type hypersensitivity (DTH) response, which reflects cell-mediated immunity were increased
significantly in both 10 or 30% CR groups. 30% CR also reduced prostaglandine E2 (PGE2)production and the Tcell proliferative response to ant-CD3. More ever the observed that proliferative T-cell response to T-cell receptor
antibody and T-cell mitogens were increased in both 10 and 30% CR groups. They concluded that CR can improve
T-cell function in human as well [25]. Pali AA et al compared the immune function of 12 obese adolescents with
healthy normal weights. They found that IFN- γ/ IL-4 ratio in CD4+ cells was higher in obese individuals. The
proposed the idea that the antigen presenting cell-regulatory T-cell-CD4+ lymphocyte axis might be affected by
calorie disturbance [26]. In a randomized controlled trial sponsored by National Institute on Aging (U.S.A), effect of
CR on human has been studied. The preliminary results showed that 20-25% CR for 6-12 months reduced leptin, T3
and fasting insulin level. CR also reduced DNA damages as a marker of oxidative insult [27]. Fraser D.A. et al
performed series of studies on the effect of fasting on rheumatoid arthritis patients. Rheumatoid arthritis is an
autoimmune disease which shared immunological features with MS. They reported that 7-day fasting reduced CD4+
lymphocyte activity and induced IL-4 production [28]. Latifynia et al. assessed the effect of Ramadan fasting on
innate immunity (neutrophil tetrazolium reaction and phagocytosis opsonization). They conducted that the innate
immune response increases after fasting [29].
Fasting and multiple sclerosis
Due to the best of our knowledge, there are only two studies on Ramadan fasting in MS patients. El-Dayem and
Zyton performed a study on 30 MS patients (15-45 years) with disability status scale (EDSS) <3. After one year, no
significant differences were observed in relapsing rate, EDSS score, and gadolinium enhanced lesions on MRI
between fasted and not-fasted groups [30]. Saadatnia et al. performed a study on 80 patients (>17 years) with EDSS
≤3. After 6 months, no significant differences in EDSS or frequency of clinical relapses were noted between fasted
and not fasted groups. The authors concluded that fasting does not impose unfavorable effect in short term. The
authors also stated that, the reduction of food intake especially of fat during Ramadan might enhance antioxidative
activity and consequently may protect against relapse after the end of Ramadan. The authors also suggested that the
reduction of uric acid level during Ramadan fasting could protect against MS relapse. Uric acid is formed as a
metabolite of purine. It also concentrated following dehydration during fasting. Serum uric acid level was lower in
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MS patients, comparing to healthy individuals [31] . In the followings we presented the concise extract from the
points discussed in the mini symposium.
Question 1: Is it safe for MS patients to fast?
Although the effect of fasting on MS is not clear, Islamic fasting is generally considered to be safe in most MS
patients. However, making a general recommendation about the safety of fasting to MS patients is not possible.
Decision should be made with respect to individual conditions. According to previous studies, Ramadan fasting does
not have negative effect on MS patients with mild disability in short term [30-31]. Patients should be monitored for
individual clinical symptoms (e.g. fatigue, energy level …), type of MS, level of disability, systemic disease,
medication, and social level. Patients’ education is an important part of management. They should be informed
about symptoms of exacerbation.
Question 2: does fasting affect MS symptoms?
One of the main concerns is whether fasting affects MS symptoms. Although previous studies reported no shortterm unfavorable effect of fasting on course of disease [30-31]; it is believed that during fast time, some of the
symptoms of MS might worsen. However, they return to the usual level during feast time. The symptoms include:
fatigue, dizziness, spasticity, cognitive problems, weakness, vision, balance, and gait.
In Previous studies on healthy adults, fasting induced fatigue and also fatigue perception. In a study performed to
assess the effect of Ramadan fasting on muscle power and fatigue in healthy football playerafter 2 and 4 weeks of
fasting, muscle power was decreased and fatigue was increased in evening. Moreover, perceived exertion and
fatigue is higher during Ramadan [32]. It seems that in MS patients who spiritually believe in fasting, perceived
fatigue is less common. However in patients who observe fasting as an obligation, perceived fatigue might be more
prevalent. More ever, heavy workers complain about tiredness and dizziness during Ramadan fasting which may be
due to dehydration [33].
According to previous studies fasting had no effect on vision in healthy adults. In healthy middle-aged volunteers,
fasting does not affect intraocular pressure, refractive error or visual activity values[34]. However, it is believed that,
unlike healthy adults, fasting might affect vision in MS patients.
8
In a study on judo athletes, Ramadan fasting had negative effect on the postural control. During Ramadan, the
unipodal (on one foot) and bipodal sway velocity was decreased in judo athletes [35].
Studies on the effects of Ramadan fasting on the mood profile stated mixed results. In a study on 8 middle-distance
runners, 30 days fast negatively affect mood profile [36]. In contrast, in another study on 20 young football players,
mood profile did not show significant differences during and after Ramadan comparing before Ramadan [37].
In another study on healthy athletes, the changes in cognitive functions were studied during Ramadan. Cognition
domains include: Psychomotor functions, vigilance, visual learning, verbal learning, memory, and executive
function. Comparison of cognitive function in the morning with the afternoon showed significant decline in
psychomotor function, visual and verbal learning and memory. The effect size was greater during Ramadan [38].
Question 3: Does fasting affect MS exacerbation?
It is also believed that according to current evidences, Ramadan fasting neither protect nor provoke MS attacks.
However, more prospective studies are needed to follow clinical conditions after Ramadan.
Question 4: Do symptomatic treatments prohibit fasting?
One of the other most frequently asked question about fasting in MS patients is whether symptomatic treatments
prohibit fasting. It is believed that, for some drugs amending the drug regimen is possible during Ramadan by
substituting oral agents with injection, prescribing slow-release or long-acting drugs once or twice at night.
However, accurate distribution of drugs which prescribed twice a day or three times per day between suhoor and
Iftar is difficult to achieve. When dosing and the time span between the doses are changed, alteration might affect
the serum level of drug and consequently its tolerance and efficacy [3]. Furthermore, drug-food interactions might
result in delayed, reduced or increased bioavailability of a drug. Also, changes in circadian rhythm, sleep
disturbances, emotional and physical stress might influence the drug pharmacokinetics. In a study even the change
in the timing of a single dose of valproate (800 mg) during Ramadan, increased the frequency of seizure
significantly [39]. The problem becomes more notable in patients on polytherapy. Table 1 summarized the
circadian variation in pharmacodynamics and pharmacokinetics of mostly prescribed medication in MS, as well as
their drug-food interaction
9
It is believed that for patients on high dose of antispastic drugs or antiepileptic drugs and patients who are obliged to
take their drugs more than twice a day, fasting is not feasible. Similarly if changing the drug has negative effect on
activity of daily living or level of disability, fasting should be avoided. There is also a general consensus that
amending the drug regimen should be started before Ramadan. In a study on 114 epileptic patients, amending drug
regimen according to timing of Suhoor and Iftar did not prevent from an increase in seizure frequency [40].
Question 5: Does consuming disease modifying drugs (DMD) prohibit fasting?
Another important question is whether consuming disease modifying drugs (DMD prohibit fasting.
Pharmacokinetics and pharmacodynamics of Interferons and Glatiramer acetate are not affected by food
consumption and it seems that plasma drug concentration-time curve of the Interferons and Glatiramer acetate did
not affected by prolonged fasting [41-42]. Up to the best of our knowledge no data is available about the effect of
fasting on Fingolimod pharmacokinetics and pharmacodynamics. However, according to neurologists view fasting is
not recommended for patients who experience severe flu-like symptoms (fever, chills, sweating, muscle aches,
fatigue) following injection.
Fasting might affect pharmacokinetics and pharmacodynamics of immunosuppressants. Also, drug-food interactions
may result in increased, or reduced and delayed systemic availability of immunosuppressants. Table 2 represented
the effects of fasting on pharmacokinetics and pharmacodynamics of immunosuppressants and manufacturer’s
recommendation for their consumption [43]. No pharmacokinetics and pharmacodynamics reactions between
cyclophosphamide and foods were reported. However, as cyclophosphamide is mainly excreted by urine, limited
access to liquids during fasting may have negative effect on the drug level [44].
Question 6: Is the level of disability (EDSS score) important when a patient decides to fast?
Whether the level of disability (EDSS score) is also important when a patient decide to fast, was also discussed. As
mentioned before, considering Saadatnia et al. and El-Dayem result, fasting is known to be safe in patients with mild
disability (EDSS≤ 3). Patients with higher levels of disability are less physically active, and consequently are more
prone to constipation, upper urinary tract infection, bedsore, and diverticulitis. Dehydration during prolonged fasting
might potentially aggravate the mentioned symptoms. It is recommended that patients with EDSS≥7 avoid fasting.
Question 7: Does the type of MS interfere with your decision about fasting?
10
It is believed that regardless of type of MS, patients with highly active disease should be prohibited from fasting.
Also patients who experienced attacks during or after Ramadan fasting should avoid fasting. During attacks, due to
high dose of corticosteroid therapy, fasting is not recommended.
Question 8: Is fasting during summer safe for MS patients?
The duration of fasting is another concern. The fasting demands at high latitudes during winter is different from
those at equatorial region during summer [45]. Increasing the number of fasting hours during summer, may increase
the negative impacts of fasting. Individualized monitoring of MS patients who observed fasting during summer and
avoiding dehydration is recommended.
Question 9: Is it safe for MS patients to fast for a whole month?
Also the interval between fasting days should be set according to patient’s individual condition. Appropriate sleep,
adequate and proper food and fluid intake during feast hours are recommended. According to Saadatnia et al. results,
fasting for 13 hours a day for 28 days has no unfavorable short-term effects [31].
Summary
Fasting during the holy month of Ramadan is a respected obligation for the healthy Muslim adults. Fasting in MS
patients has recently attracted the physicians’ attention. The experimental studies were focused on protective role of
intermittent fasting in MS. Human studies on fasting in MS patients, especially Islamic fasting are very rare. So far
there are insufficient evidences to suggest fasting may be effective in protecting against or controlling MS signs.
However, according to the current evidence, fasting had no unfavorable effect on course of disease.
In current meeting, there is a general consensuses that observing Ramadan fasting is possible for many of the MS
patients. Careful monitoring of general and clinical condition, as well as precise management of drug regimen, diet,
and sleep pattern would help to reduce possible negative effects of fasting. However, in the following situations
fasting is not recommended:
1.
During attacks
2.
Patients on high dose of antispastic and anticonvulsant drugs
3.
Patients with coagulopathy
11
4.
Patients with EDSS≥7
5.
Patients with active disease
Fasting especially during summer might negatively affect fatigue, weakness, vision, balance, and gait.
Individualized recommendation should be made with respect to energy level and general well being of the patient. It
seems that MS patients who spiritually believed in fasting as a sacred obligation, report fewer negative impact of
fasting on MS signs. For example, perceived fatigue is increased during fasting. Spiritual belief might reduce fatigue
perception. This hypothesis might be expandable to other symptoms of the disease. On the other hand, in patients
who find themselves obliged to fast, the perception of negative impacts of fasting might be higher. Patients should
be provided with scientific evidence about the effects of fasting on health issues before Ramadan to decide about
fasting themselves.
More researches are needed to prepare a detailed guideline for MS patients. Our meeting is an attempt to help
physicians for better management of MS patients who decide to fast, as well as to pave the ground for more
researches in this field.
List of abbreviations
AA: acetoacetate
ADF: Alternate-day fasting
CNS: Central nervous system
CR: Calorie restriction
DMD: Disease modifying drugs
EAE: Experimental Autoimmune Encephalomyelitis
EDSS: Expanded disability status scale
HNE: 4-hydroxynonenal
KD: ketogenic diet
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IFN-γ: Interferon gamma
IL-6: Interleukin 6
MDA: malondialdehyde
MS: Multiple sclerosis
NFkB: nuclear factor kB
Th-17: T-helper 17
TGF-β: Transforming growth factor beta
TNF-α: tumor necrotizing factor α
Competing interests
None of the authors had any financial or personal conflicts of interests.
Authors’ contribution
Since it was an expert meeting, all authors contributed to the article equally and their names are presented in
alphabetic order.
SRJ: wrote the primary draft
MAS: Proposed the idea, revised the primary draft
Acknowledgements
The meeting and accommodations was supported by an unrestricted educational grant from CinnaGen Company.
The authors would like to thank the sponsor for the logistic support during the meeting and also thank the “Research
Development Center” of Sina hospital in for language editing of the manuscript
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Table 1: Circadian variation in pharmacodynamics and pharmacokinetics, as well as, drug-food interaction of most
commonly prescribed MS drugs
Drug
Food-drug interaction
Baclofen
No effect [46]
Dantrolene
No effect [47]
Pregabalin
Consuming with food decreased the
Recommendation
cmax by 25-30% and delay tmax by
about 3h [48]
Tizanidine
Simultaneous food intake with
Extent of absorption is increased up to 20% relative
capsule reduced the cmax and the
to administration of the capsule under fasted
AUC o-t by less than 20% and
conditions.
extends tmax from 0.75 h to 1.5 h.
In contrast Simultaneous food
The tablet and capsule dosage forms are not
consumption with tablet increased
bioequivalent when administered with food.
cmax and the AUC o-t by 22.6% and
Food increases both the time to peak concentration
45.2% respectively [49]
and the extent of absorption for both the tablet and
capsule. However, maximal concentrations of
tizanidine achieved when administered with food
were increased by 30% for the tablet, but decreased
by 20% for the capsule. Under fed conditions, the
capsule is approximately 80% bioavailable relative to
the tablet.
Using tizaniidine together with caffeine is generally
not recommended. Combining these medications may
significantly increase the blood levels and effects of
tizanidine.
17
Gabapentin
High protein food increased AUC
Take extended release tablet with evening meal.
and cmax by 26% and 32%
Swallow whole; do not chew, crush, or split.
respectively [50]
No significant effect on rate or extent
of absorption of immediate release
tablet
Increases rate and extent of
absorption of extended release tablet
Carbamazepi
Carbamazepine serum levels may be
Extended release tablets should be administered with
ne
increased if taken with food and/or
meals; swallow whole, do not crush or chew.
grapefruit juice.
SSRIs
Paroxetine: Peak concentration is
increased, but bioavailability is not
significantly altered by food
Sertraline: Average peak serum
levels may be increased if taken with
food.
AUC o-t , area under curve from administration (0) to last observed concentration at (t), cmax, maximum
concentration, tmax, the time after administration of a drug when the maximum plasma concentration is reached
18
Table 2: Effect of fasting on pharmacokinetics and pharmacodynamics of immunosuppressants and manufacturer’s
recommendation for their consumption
Drug
circadian variation in
manufacturer’s recommendation
pharmacodynamics and
pharmacokinetics
Azathioprine
Taking after meals or in divided doses for decreasing
stomach upset
Cyclophosphamide
On an empty stomach with a glass of water or juice
or with food
Tablets are not scored and should not be cut or
crushed. To minimize the risk of bladder irritation, do
not administer tablets at bedtime.
Methotrexate
Methotrexate peak serum
On empty stomach with plenty of water
levels may be decreased if
limit or avoid caffeine intake if you are taking
taken with food.
methotrexate. Avoid drinks, foods, or diet pills that
Milk-rich foods may decrease
contain caffeine, such as coffee, tea, cola, and
methotrexate absorption.
chocolate.
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