INTRODUCTION

 

Multiple sclerosis (MS) is the most common disabling neurologic disease of young people. MS affects approximately 1,000000  people worldwide. MS typically presents between the ages of 18 and 45, although the true onset of the disease likely predates the initial symptoms in most individuals.¹

Ramadan is the month in which Muslims are ordained to fast every year. Fasting is an act of worship; it represents the fourth pillar of Islam. It involves abstaining from all intakes and from sexual intercourse from Dawn till sunset.² Upon reaching puberty, all healthy Muslims are required to partake in the fast. Individuals who are sick, traveling, pregnant, breast-feeding, menstruating, or debilitated are exempt from fasting.³ However, many Muslims who are eligible for exemption choose to fast nonetheless.⁴

Due to the fact that the Islamic calendar (Hijri) is a lunar calendar, the first day of Ramadan advances 11 days each year in relation to the Gregorian calendar. Consequently, Ramadan falls on different parts of the seasonal year over a 33-year cycle. This seasonal shift dramatically impacts the amount of daily fasting time that occurs in any given location. Moreover, a location’s latitudinal distance from the equator also substantially impacts daily fasting time. While the average fast period during Ramadan is 12 hours in length⁵, it can be as long as

 

22 hours in Polar Regions during summertime.⁶ Fortunately, Muslims living in such regions are permitted to adopt the fast period of either Mecca or the nearest temperate location .⁷

During the fasting month, many physiological and biochemical changes occur that might be due to alteration in eating and sleeping patterns .⁸ It is a challenge for Muslim MS patients to decide whether or not to fast as they do not know whether prolonged abstinence from food and drink could have an unfavorable impact on the course of their disease.⁹ Frequently, they ask their physicians certain questions pertaining to their ability to fast safely. Others may decide to observe the fasting on their own accord but they may seek advice on how to adjust their life style and medication to suit the fasting. Whatever the case, physicians ought to have an updated working knowledge about medical implications of fasting on MS.¹⁰

The effects of fasting on multiple sclerosis have not been adequately investigated and little is known about this topic. The aim of this study is to elucidate the effects of Ramadan fasting on MS activity and severity.

 

SUBJECTS AND METHODS

 

This study was conducted between July 2010 and July 2011. Thirty patients with clinically definite multiple sclerosis according to criteria proposed by McDonald et al.¹¹ were enrolled into the study after obtaining  informed written consent. All MS patients were of relapsing remitting type. Relapsing- remitting (RR) MS is defined by the occurrence of clearly defined disease relapses with full recovery or with sequel and residual deficit upon recovery; periods between disease relapses are characterized by lack of disease progression.¹²

The patients were classified into two groups; fifteen patients who fasted the month of Ramadan and the other fifteen patients who did not fast and considered as control group. The two groups were matched for age, sex, EDSS and relapse rate before entering the study.  All patients were followed for 1 year after Ramadan regarding their EDSS, relapsing rate, gadolinium enhanced lesions on MRI.

 

Exclusion criteria:

1.      The age of the patients less than 15 years to exclude other causes of white matter disease in young age (e.g. leucodystrophy) and patients above 45 years were also ruled out to make sure that other causes of white matter lesions were not present (e.g. arteriosclerosis, Binswanger,s disease, Alzheimer,s disease and hypertensive encephalopathy).¹³

2.      Patients with moderate to severe disability (EDSS> 3) because their disability interfere with ability to fast for a long time.

3.      Patients having any medical, cardiological, endocrinal, hepatic, and renal or history suggestive of collagen disorders were excluded from the study.

4.      Patients on medications, other than treatment of MS for at least 6 months before the study were excluded.

 

All patients were submitted to the following battery of assessment:

A)           Clinical evaluation:

1.   History taking, with special stress on:

·           Age at onset of the disease.

·          Annualized relapse rate.

·          Disease duration.

·          Associated diseases (All patients had been asked for history of other autoimmune diseases, organ failure or infection).

·          History of drug intake was taken in details especially drugs that have immunological effects e.g. corticosteroids.

2.   General and full neurological examination

·          General examination of other systems was performed to exclude diseases that could have effect on the disease course.

·          Full neurological examination.

·          Assessment of disability by the use of Expanded Disability Status Scale (EDSS).¹⁴ The EDSS is scored according to the degree of affection in the functional systems.¹⁴

 

B)           Magnetic Resonance Imaging (MRI):

Cranial (MRI) and in patients with spinal affection, spinal (MRI) were performed with 1.5 Tesla scanner. In all studies, axial, coronal and sagittal slices were done. Axial 5 mm thickness slices obtained through the brain from the foramen magnum to the higher convexity and spinal cord with proton density and T2 weighted spine echo (SE) image before contrast, and T1 weighted SE before and after contrast (i.e. after administration of an intravenous bolus of 10 mL of 0.5-mol/L gadolinium-diethyl-triaminepentaacetic acid (Gd-DTPA). MRI criteria of Barkhof were followed in the diagnosis of MS.¹⁵

 

C)           Laboratory investigations:

All patients were subjected to the following:

a)   Routine laboratory investigations:

·              Complete blood count.

·              Fasting and post prandial blood sugar.

·              Kidney function test.

·              Liver function tests.

·              Thyroid function tests.

Patients with abnormal laboratory investigations were excluded from the study.

b)      Immunological investigations: Cerebro-spinal fluid (CSF) analysis.

 

Statistical Analysis

The collected data were computed and analyzed using SSPS program V16, showing the following rules: mean value, standard deviation (SD) and chi-squared distribution. P value of < 0.05 was considered statistically significant. Then the results had been presented in the following tables.

 

RESULTS

 

A total of 30 patients were studied over a period of one year. During Ramadan, 15 patients were fasting and 15 patients were not fasting. The clinical and MRI characteristics of all patients at the entry of the study are shown in (Table 1). The age distribution of patients was not significantly different between the 2 groups (P>0.05). Mean age at the onset of MS was 30.73±7.42 y for fasting group and 31.13±5.31 y for the non fasting group. There was no statistical significant difference in the sex ratio between the two groups (P>0.05). Also, there was no significant difference in the mean baseline annualized relapsing rate, disease duration, EDSS score and frequency of gadolinium enhanced lesions on MRI between the two groups (P>0.05).

The clinical and MRI characteristics of all patients after one year are shown in (Table 2). There was no significant difference in the mean annualized relapsing rate, EDSS score and frequency of gadolinium enhanced lesions on MRI between the two groups (P>0.05).

 

 

Table 1.  Clinical and MRI findings in both fasting and non fasting groups at the entry of the study.

 

	Fasting (No. 15)	Non fasting (No. 15)	Significance
Age (mean ±SD)	30.73±7.42	31.13±5.31	NS
Sex (female to male ratio)	9/6	9/6	NS
R (mean ±SD)	2.53±0.51	2.43±0.52	NS
D (mean ±SD)	4.13±1.30	4±1.41	NS
EDSS (mean ±SD)	2.46±0.51	2.53±0.48	NS
GAe (+/-)	5/10	6/9	NS

EDSS expanded disability status score; D disease duration; GAe gadolinium enhanced lesions on MRI; R annualized relapsing rate.

 

Table 2. Clinical and MRI findings in both fasting and non fasting groups after one year.

 

	Fasting (No. 15)	Non fasting (No. 15)	Significance
R (mean ±SD)	2.63±0.45	2.73±0.45	NS
EDSS (mean ±SD)	2.60±0.54	2.66±0.44	NS
GAe (+/-)	6/9	7/8	NS

EDSS expanded disability status score; GAe gadolinium enhanced lesions on MRI; R annualized relapsing rate.

 

 

DISCUSSION

 

In this study, there was no significant difference between fasting and non-fasting groups after one year regarding annualized relapse rate, EDSS and gadolinium enhanced lesions on MRI. A prospective study to determine the effects of prolonged intermittent fasting on the course of multiple sclerosis in a cohort of patients was recently reported .¹⁶ At the end of the study, no significant changes in the scores or the frequency of clinical relapses were detected between the 2 groups (p>0.05). It was concluded that fasting had no short-term unfavorable effects on the disease course in MS patients with mild disability.¹⁶

Recent data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis.¹⁷ The exact mechanisms responsible for increased oxidative stress in MS patients needs to be further explored.¹⁸

Sadatania et al.¹⁶ stated that fasting during Ramadan may increase antioxidant activity. This is because fasting restrict fat intake, which is associated with a marked reduction in low –density lipoprotein levels, the mean high –density lipoprotein cholesterol level, however, increased significantly during Ramadan .^19,20 Fat acts as an oxidant insult in the body; high fat meals impair macrovascular endothelial function and are also linked to increased oxidative stress. The diminished food intake during Ramadan, especially that of fats which further lowers low –density lipoprotein levels, might increase antioxidant activity and consequently could protect against relapse after the end of the fasting month.¹⁶

Uric acid is formed as a product from purine metabolism and during Ramadan with weight loss it is postulated that this factor and the concomitant dehydration while fasting may lead to raised uric acid levels .²¹ A number of studies have demonstrated that patients with MS have low serum levels of uric acid; therefore, elevated serum uric acid levels during Ramadan may confer protection against MS relapse.¹⁶

Podikoglou et al.²² investigated the possibility of a deficiency in host-defense mechanisms in MS patients by examining the polymorphonuclear leucocytes (PMNLs) functions in these patients. In a cross examination experiment these authors found that the presence of MS serum inhibits the adherence and chemotaxis of control PMNLs and, conversely, the presence of control serum restores the adherence and chemotaxis of patients PMNLs. This led to the hypothesis that there might be one or more factors that obstruct the adherence and chemotaxis of patients PLMNLs. These results demonstrated that MS patients have significant in vitro disorders of their PMLN functions compared with healthy controls.

In a recent study, Afshineh Latifynia et al.²³ examined the effect of fasting during the month of Ramadan on innate immune function (phagocytosis, opsonization, and neutrophil tetrazolium reduction) in a group of 13 males. The main emphasis of this study was to elucidate the effect of fasting during Ramadan on neutrophil function  (innate immunity). The study concluded that the innate immune response does not decrease, in fact increases after fasting, which may be an important, beneficial effect in Muslims fasting during Ramadan.

In conclusion, Ramadan fasting has no effects on MS activity and severity. However, there is lack of consensus regarding the effects of Ramadan fasting on MS biomarkers.

 

[Disclosure: Authors report no conflict of interest]

 

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