Nutritional Neuroscience

An International Journal on Nutrition, Diet and Nervous System

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ynns20

Nutritional intake and its impact on patients with

epilepsy: an analytical cross-sectional study

Rania Shehata Ismail, Nirmeen Adel Kishk, Hoda Ibrahim Rizk, Thanaa El-
Kholy, Lamiaa M. Abd El-Maoula, Ola Ibrahim El-Desoky, Shaimaa Shaheen &
Enji El-Sawy

To cite this article: Rania Shehata Ismail, Nirmeen Adel Kishk, Hoda Ibrahim Rizk, Thanaa El-
Kholy, Lamiaa M. Abd El-Maoula, Ola Ibrahim El-Desoky, Shaimaa Shaheen & Enji El-Sawy
(2021): Nutritional intake and its impact on patients with epilepsy: an analytical cross-sectional
study, Nutritional Neuroscience, DOI: 10.1080/1028415X.2021.1905371

To link to this article: https://doi.org/10.1080/1028415X.2021.1905371

Published online: 29 Mar 2021.

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NUTRITIONAL NEUROSCIENCE
https://doi.org/10.1080/1028415X.2021.1905371

Nutritional intake and its impact on patients with epilepsy: an analytical

cross-sectional study
Rania Shehata Ismaila, Nirmeen Adel Kishk a, Hoda Ibrahim Rizkb, Thanaa El-Kholyc, Lamiaa M. Abd El-Maoulac,
Ola Ibrahim El-Desokyc, Shaimaa Shaheena and Enji El-Sawya
a
Neurology Department, Faculty of Medicine, Cairo University, Giza, Egypt; bPublic Health and Community Medicine Department, Faculty of
Medicine, Cairo University, Giza, Egypt; cNutrition and Food Science Department, Faculty of Home Economics, Al-Azhar University, Tanta,
Cairo, Egypt

ABSTRACT KEYWORDS
Background: Anecdotal reports have proposed that diet might influence the occurrence of Epilepsy; seizure control;
seizures. nutritional assessment;
Objectives: Our objectives were to assess nutritional status in a sample of patients with epilepsy dietary intake;
and to investigate the impact of nutrition on epilepsy control. macronutrients;
micronutrients
Patients and methods: One hundred and fifty patients with epilepsy participated in the study. To
assess nutritional status, sociodemographic characteristics, anthropometric measurements, dietary
food intake, and 24-hour food intake were evaluated. Patients answered questions using a food
frequency questionnaire.
Results: In patients with epilepsy, there was insufficient intake of water, fiber, potassium, magnesium
and some vitamins (C, E, B12, folate and niacin); suboptimal intake of calories, zinc, calcium, and some
vitamins (A, B1 and B6); optimal intake of total fats; and over-intake of proteins, carbohydrates,
phosphorus, iron, sodium, and vitamins D and B2. Moreover, there was a statistically significant
difference between patients with controlled versus uncontrolled seizures regarding frequency of
vegetable intake and percentage of caloric intake from the recommended dietary allowance.
Stepwise logistic regression indicated that those with low intake of vegetables had a 2.3 times
higher likelihood of uncontrolled seizure occurrence compared to those with a high intake of
vegetables per week. Also, those with optimal caloric intake were 80% less likely to have
uncontrolled seizures than those with too much caloric intake.
Conclusion: Macro- and micronutrient intake were unbalanced in patients with epilepsy. Patients who
consumed too many calories and too few vegetables were more likely to have improper seizure control.

1. Introduction relationship between food and seizures. Foods are com-

monly considered provoking agents for seizures, and
Epilepsy is one of the most common neurological dis-
proper nutritional intake can be considered therapeutic
eases in the world [1], affecting 0.5–1% of the world’s
[6]. A ketogenic diet is one of the recommended methods
population [2]. Several theories have been suggested to
to control epilepsy in some drug-resistant cases [7].
explain the pathogenesis of epilepsy, one of which is
Many researchers have investigated nutritional status
related to nutrition [3].
in children with epilepsy. However, very few studies
Nutritional factors are involved in the regulation of elec-
have assessed nutrition in adult patients with epilepsy.
trical activity in the brain. Severe deficiency of thiamin, pyr-
This study was designed to assess nutritional status in
idoxine, vitamin D, calcium, magnesium (Mg) and
a sample of patients with epilepsy and to investigate
carnitine can cause seizures. A subnormal concentration
the impact of nutrition on epilepsy control.
of each of these nutrients is common in patients with epi-
lepsy, for example, in vitamin B6-dependent epilepsy, a
condition in which intractable seizures can be controlled 2. Patients and methods
by administration of large doses of vitamin B6 [4]. Proper
2.1. Study design and participants
intake of copper, zinc, and selenium is important for anti-
oxidant function and eradication of free radicals, for nor- This was an analytic cross sectional study conducted on
mal brain function and to control epilepsy [5]. 150 Egyptian patients with epilepsy, carried out from
In epilepsy outpatient clinics, patients are frequently May 2018 to June 2020 in Epilepsy unit, Cairo university
asked about what foods they eat to explore the Hospital. The study included patients of both genders

CONTACT Rania Shehata Ismail raniashehata.neuro@yahoo.com Alsaray street, ELManial, Cairo 11956 Egypt
This article has been republished with minor changes. These changes do not impact the academic content of the article.
© 2021 Informa UK Limited, trading as Taylor & Francis Group
2 R. S. ISMAIL ET AL.
aged over 13 years who had epilepsy for at least 1 year,
according to the International League Against Epilepsy
(ILAE) 2017 classification [8]. Patients were excluded if
they were non-compliant, had combined true and
pseudo seizures, had a disease-causing significant nutri-
tional status impairment (malignancy, chronic infec-
tions), had an endocrinal disorder causing alterations
in energy metabolism (hyper-hypothyroidism), diabetic
patients, patients on specific dietary regimens such as
ketogenic diet or were pregnant or lactating at the time
of the study.
Flow diagram for the eligible and excluded people
with epilepsy is illustrated in (Figure 1).
2.2. Sampling
All patients who attended the outpatient neurology
clinic in Cairo university hospital over a 4 month period
who fulfilled the inclusion criteria and agreed to partici-
pate in the study were included (150 patients).
2.3. Data collection tools and methods
All patients were subjected to the following:
. Careful clinical assessment with special emphasis on
age at onset and duration of epilepsy, seizure semiology,
seizure frequency, antiepileptic treatment, family his-
tory of epilepsy, and history of febrile convulsions
. Categorization of patients as controlled or not
according to Kwan et al. [9] who defined ‘seizure
Figure 1. Flow diagram for the eligible and excluded people
with epilepsy.
control’ as the absence of consecutive seizures in
the previous 12 months
. Interview questionnaires for nutritional assessment,
which contained several sections, including
▪ Sociodemographic data: It collected data on individ-
ual characteristics such as age, educational and occu-
pational status of the patient and salary per month.
▪ Anthropometric measurements: Included weight,
height, waist circumference, hip circumference,
and body mass index (BMI), which was calculated
using the formula BMI (kg/m2) = BW (kg)/BH2
(m2).
▪ Dietary intake: The patients were asked about
every food, drink, or snack consumed and the
amount in units or parts, and then the researcher
changed these units or parts into grams to calcu-
late the daily intake of different nutrients [10].
▪ 24-hour food intake: The mean of 3 days food intake
data was analyzed based on food composition tables
[11]. Results were compared with current rec-
ommendations for nutrient intake (diet adequacy
was estimated by using dietary reference intakes
for energy, carbohydrates, fiber, fat, fatty acids,
cholesterol, protein and amino acids) [12].
▪ Dietary pattern food frequency questionnaire: This
was used to obtain qualitative descriptive infor-
mation about usual food and beverage consump-
tion patterns per week for patients with epilepsy,
including
- Energy foods: Cereals, oils, fats, sugar and sweets
- Tissue building foods: Meat, chicken, fish, eggs,
legumes, milk and its products
- Fruit and vegetables
- Beverages: Tea, coffee, milk, energy drinks, cola, and
fruit juice. We used ‘standard’ portion sizes and par-
ticipants were simply asked how often they ate from
these food groups per day, week and month [13].
. Percent nutrients intake from the RDA(rec-
ommended dietary allowance) according to age and
sex of the patients was classified as:Insufficient intake
<75% from the RDASuboptimal intake 75–<100%
from the RDAOptimal intake 100–<120% from the
RDAOver intake >120% from the RDA
2.4. Statistical analysis
Data were analyzed using IBM SPSS (Statistical Package
for Social Sciences version) version 23. The Kolmo-
gorov–Smirnov test was used to assess the normal distri-
bution of the variables. Quantitative data were described
as mean and standard deviation or median and interquar-
tile range (IQR), whereas qualitative data were presented
by frequency. Chi-squared test and Fisher’s exact test
 NUTRITIONAL NEUROSCIENCE 3

were used to detect differences between qualitative vari- 3. Results

ables. Independent sample t-test and Mann–Whitney
test were used to detect differences between quantitative
variables. Pearson and Spearman correlation analyses
were used to test correlations between variables. Stepwise
logistic regression was used to detect the nutritional pre-
dictors of uncontrolled seizures. P-value < 0.05 was con-
sidered statistically significant.
2.5. Ethical considerations
The study proposal was approved by the Ethical Com-
mittee of Department of Neurology, Faculty of
Medicine, Cairo University. Our research proposal was
approved on 25 April 2018. The aim, procedures of the
study, the data confidentiality, as well as the impact of
the study was explained to every participant. The
researcher confirmed that participation in the study
was voluntary and informed consent was obtained before
patients were enrolled in the study. All procedures were
performed in accordance with the Declaration of
Helsinki.
3.1. Descriptive results
3.1.1. Sociodemographic characteristics of patients
Patients with controlled seizures included 28 (35.4%)
males and 29 (40.8%) females. Their ages ranged from
13 to 71 years, median = 30 years and IQR = 25–41.
Patients with uncontrolled seizures included 51
(64.6%) males and 42 (59.2%) females, and their ages
ranged from 13 to 61 years, median = 31 and IQR =
25–37. There was no statistically significant difference
between patients with controlled versus uncontrolled
seizures regarding age and gender (P = 0.98, 0.52,
respectively). They were also matched regarding type
and etiology of seizures (P-value = 0.13, 0.32), respect-
ively. Sociodemographic characteristics and personal
habits of patients are shown in Table 1.
3.1.2. Anthropometric and clinical findings of
patients
According to BMI, four patients (3.1%) were under-
weight, 47 (36.7%) were normal weight, 31 (24.2%) were

Table 1. Patient sociodemographic characteristics and personal habits.

Age Range: 13–71years
Median: 30.50
IQR: 25–38

Gender n% M: 79 (52.7%)
F: 71 (46.7%)

Occupation n% Working 33 (22%)

Not working 117 (78%)

Smoking n% Yes 18 (12%)

No 130 (86.7%)
Ex-smokers 2 (1.3%)

Drug addiction n% Yes 2 (1.4%)

No 148 (98.7%)

*Salary per month n% <1000 81 (54%)

By Egyptian pound 1000–2000 49 (32.7%)
2000–3000 8 (5.3 %)
3000–5000 2 (1.3%)
>5000 2 (1.3%)

**Sports Frequency per week n% 0 131 (87.3%)

1 4 (2.7%)
3 4 (2.7%)
5 4 (2.7%)

***Education n% Illiterate 73 (48.75%)

Primary and preparatory 39 (26%)
Secondary education 21 (14%)
University education 7 (4.7%)

Number of meals/day n% <3meals/day 89 (59.3%)

3meals/day 54 (36%)
>3meals/day 7 (4.7%)

****Outdoor feeding n% Yes 14 (9.3%)

no 133 (88.7%)
Note: *8 missing data, ** 7 missing data, ***10 missing data, **** 3 missing data.
4 R. S. ISMAIL ET AL.

Table 2. Patient anthropometric and clinical findings.

Weight (kg) 76 ± 20
Height (cm) 165 ± 9
BMI (kg/m2) 28 ± 6
Underweight n% 4(3.1%)
Normal weight n% 47 (36.7%)
Overweight n% 31 (24.2%)
Obese n% 46 (35.9%)
Waist circumference (cm) 90 ± 16
Hip circumference (cm) 104 ± 16

Age at onset (Years) Range:0.08–45

Median:12
IQR: 8–19

Type of seizures n% Focal 71 (47%)

Generalized 79 (52.7%)

Etiology of seizures n% Idiopathic 84 (56%)

Genetic 28 (18.7%)

Symptomatic 38 (25.3%) Congenital and birth injuries 18 (12%)

Vascular 6 (4%)
Traumatic 11 (7.3%)
Neoplastic 3 (2%)

*Number of AEDs n% Monotherapy 60 valproate: 20 (13.3%)

(40%) levetiracetam:14 (9.3%)
carbamazepine: 18 (12%)
diphenylhydantoin: 7 (4.7%)
lamotrigine:1 (0.7%)
Polytherapy 89 (59.3%)

Epilepsy control Yes 57 (38%)

No 93 (62%)

*Status epilepticus Yes 5 (3.3%)

No 144 (96%)
*1 missing data.

overweight, and 46 (35.9%) were obese. Anthropometric
and clinical findings of patients are shown in Table 2.
3.1.3. The mean and median daily intake of
nutrients in patients with epilepsy
In patients with epilepsy, there was insufficient intake of
water, fiber, potassium, Mg and some vitamins (C, E,
B12, folate and niacin); suboptimal intake of calories,
zinc, calcium and some vitamins (A, B1 and B6); opti-
mal intake of total fats; and over-intake of proteins,
carbohydrates, phosphorus, iron, sodium, and vitamins
D and B2 (Table 3).
regarding BMI (P = 0.6). Also, there was no statisti-
cally significant difference in BMI categorization
between patients with controlled versus uncontrolled
seizures (P = 0.6).
3.2.2. Comparison of daily nutrient intake between
population subgroups distributed according to
seizure control
There was no statistically significant difference between
patients with controlled versus uncontrolled seizures
regarding the mean and median of daily nutrient intake
(Table 4).

3.2.3. Comparison of percentage of nutrient intake

3.2. Comparative results
3.2.1. Comparison of BMI between population
subgroups distributed according to seizure control
The BMI mean in patients with controlled seizures
was 27.4 ± 5.6, whereas in patients with uncon-
trolled seizures it was 28.07 ± 6.94. There was no
statistically significant difference between patients
with controlled versus uncontrolled seizures
from the recommended dietary allowance (RDA)
between population subgroups distributed
according to seizure control
A statistically significant difference was found regarding
percentage of caloric intake from RDA between popu-
lation subgroups distributed according to seizure control.
Seventy-seven percent of patients with uncontrolled sei-
zures had too much caloric intake compared to only
 NUTRITIONAL NEUROSCIENCE 5

Table 3. The mean and median daily intake of nutrients in patients with epilepsy.
Nutrients Actual intake % intake from RDA
Macronutrients
Water (ml) mean ± SD 540.29 ± 234.34 17 ± 8
Calories (gm) mean ± SD 2024.04 ± 826.02 97 ± 37
Proteins (gm) mean ± SD 62.89 ± 28.65 123 ± 53
Carbohydrates (gm) mean ± SD 258.64 ± 124.63 199 ± 96
Total fats (gm) median (IQR) 75.65 (53.225–107.4) 116 (84-170)
Fiber percent mean ± SD 61.55 ± 37.45 65 ± 39

Micronutrients
Phosphorus (mg) mean ± SD 1097.4 ± 578.5 155 ± 83
Iron (mg) mean ± SD 14.1 ± 6.56 133 ± 87
Sodium (mg) mean ± SD 1875.1 ± 1008.7 126 ± 67
Potassium (mg) mean ± SD 1889.1 ± 809.5 40 ± 17
Zinc(mg) mean ± SD 9.5 ± 4.6 99 ± 47
Magnesium (mg) mean ± SD 351.2 ± 178.9 31(18-50)
Calcium(mg) median (IQR) 310.4 ± 27.7 96 ± 46
Vitamin A (mcg) median (IQR) 362.8 (178.4–693.5) 84 ± 47
Vitamin C (mg) median (IQR) 25.35 (15–70) 73 ± 37
Vitamin D (mcg) median (IQR) 0.75 (1.3–10) 308 ± 177
Vitamin E (mg) mean ± SD 64.1 ± 26.5 45 (23–84)
Folate (mcg) mean ± SD 290.9 ± 146.2 30 (15–70)
Niacin (mg) mean ± SD 12.7 ± 7.1 5 (1–10)
Vitamin B1 (mg) median (IQR) 1.10 (0.7–1.5) 92 (66–133)
Vitamin B2 (mg) median (IQR) 2(1.3–2.9) 163 (108–237)
Vitamin B6 (mg) median (IQR) 1.2 (0.6–1.5) 88 (69–115)
Vitamin B12 (mcg) median (IQR) 88.14 (0.9–2.5) 67 (41–104)
Note: RDA: recommended dietary allowance; IQR Interquartile range.

Table 4. The mean and median daily nutrient intake in patients with controlled and uncontrolled seizures.
Nutrients Controlled seizures Uncontrolled seizures P-value
Macronutrients
calories (gm) mean ± SD 1936.22 ± 705.4849 2077.86 ± 891.2948 0.31
proteins (gm) mean ± SD 60.85 ± 27.28 64.14 ± 29.53 0.49
Carbohydrates (gm) mean ± SD 240.16 ± 92.40 269.96 ± 140.06 0.16
cholesterol (gm) mean ± SD 222.87 ± 219.19 219.895 ± 219.3490 0.93
Water (ml) mean ± SD 500.28 ± 218.44 564.81 ± 241.44 0.12
Fiber intake (gm) mean ± SD 287.60 ± 134.35 292.942 ± 153.70 0.57
Fiber percent mean ± SD 71.90 ± 33.58 73.23 ± 38.42 0.05
fats Animal fat 14.9 (9.05–27.75) 19 (11.05–35.2) 0.08
Plant fat median (IQR) 47 (32.3–75.35) 53 (32.3–75.35) 0.93
Total fat 72.1 (51–109.7) 79 (54.35–107.5) 0.63
Micronutrients
Phosphorus (mg) mean ± SD 155.1 ± 97.1 155.7 ± 73.6 0.96
Iron (mg) median (IQR) 113 (69.2–183.2) 107 (61.7–189.4) 0.83
Sodium (mg) mean ± SD 123.5 ± 72.5 127.7 ± 64.4 0.72
Potassium (mg) mean ± SD 38.5 ± 15.9 41.2 ± 17.9 0.36
Zinc (mg) mean ± SD 94.9 ± 42.8 102.1 ± 50.2 0.37
Magnesium (mg) mean ± SD 93.9 ± 42.5 97.5 ± 49.5 0.65
Calcium (mg) median (IQR) 27 (15–45) 32 (18.7–54.7) 0.25
Vitamin A (mcg) median (IQR) 41 (16.3–77.7) 48 (25.7–89) 0.23
Vitamin C (mg) median (IQR) 25 (14.2–46) 36 (15.2–84.5) 0.17
Vitamin D (mcg) median (IQR) 5 (2–10.7) 5 (1.3–9.6) 0.65
Vitamin E (mg) mean ± SD 47.4 ± 28.2 45.5 ± 25.7 0.67
Folate (mcg) mean ± SD 71.9 ± 33.6 73.2 ± 38.4 0.83
Niacin (mg) mean ± SD 80.6 ± 44.3 86.5 ± 48.9 0.46
Vitamin B1 (mg) median (IQR) 92 (65.1–127.2) 100 (65.4–134.8) 0.43
Vitamin B2 (mg) median (IQR) 162 (112.2–216.8) 169 (96.2–274.8) 0.76
Vitamin B6 (mg) median (IQR) 85 (65.4–107.7) 92 (69.2–123) 0.37
Vitamin B12 (mcg) median (IQR) 63 (41.7–89.6) 71 (37.5–108.3) 0.37
Note: IQR: Inter quartile range.

23.1% of patients with controlled seizures (P = 0.005).
However, no statistically significant difference was
found between percentages of carbohydrate, protein, fat
and fiber intake from RDA between the two groups (P
= 0.58, 0.44, 0.7 and 0.17, respectively) (Table 5).
3.2.4. Frequency of macronutrient intake among
patients with controlled and uncontrolled seizures
There was a statistically significant difference between
patients with controlled versus uncontrolled seizures
regarding frequency of vegetable intake (P = 0.03).
6 R. S. ISMAIL ET AL.

Table 5. Percentage of nutrient intake from RDA in patients with controlled and uncontrolled seizures.
Nutrients % intake from the RDA Controlled seizures Uncontrolled seizures
N % N % P-value
Calories <75 17 40.5 25 59.5 *0.005
75–<100 11 29.7 26 70.3
100–<120 20 62.5 12 37.5
>120 9 23.1 30 77

Carbohydrates <75 4 44.4 5 55.6 0.58

75–<100 2 20.0 8 80.0
100–<120 3 30 7 70
>120 48 39.7 73 60.3

Proteins <75 13 46.4 15 53.6 0.44

75–<100 6 26.1 17 73.9
100–<120 6 31.6 13 68.4
>120 32 40.0 48 60.0

Fats <75 11 36.7 19 63.3 0.70

75–<100 8 40 12 60
100–<120 14 46.7 16 53.3
>120 24 34.3 46 65.7

Fibers <75 36 37.5 60 62.5 0.17

75–<100 14 53.8 12 46.2
100–<120 4 28.6 10 71.4
>120 3 21.4 11 78.6
*Statistically significant, RDA: recommended dietary allowance.

However, no statistically significant differences were
found between the groups regarding frequency of
other macronutrient intake (Table 6).
3.2.5. Comparison of outdoor feeding and number
of meals per day between population subgroups
distributed according to seizure control
There was no statistically significant difference between
patients with controlled versus uncontrolled seizures
regarding outdoor feeding, number of meals per day
(P = 0.6 and 0.7) respectively.
3.2.6. Comparison of sports frequency per week
between population subgroups distributed
according to seizure control
Fifty-two (39.7%) patients with controlled seizures did
not practice sports whereas, 79 (60.3%) patients with
uncontrolled seizures did not practice sports.

Table 6. Comparison of macronutrient frequency intake in patients with controlled and uncontrolled seizures.
Frequency of intake
more than 5
0–2 times/week 3–4 times/week times/week
Nutrients Seizure control N % N % n % P-value
Carbohydrates controlled 24 36.4 18 31.6 15 55.6 0.1
uncontrolled 42 63.4 39 68.4 12 44.4

Fats
Butter controlled 45 38.1 5 31.3 4 31.3 0.79
uncontrolled 73 61.9 11 68.8 5 55.6
Vegetable oil controlled 8 47.1 8 36.4 40 36.4 0.69
uncontrolled 9 52.9 14 63.6 70 63.6

Proteins
Meat and poultry controlled 40 40.8 12 27.9 5 55.6 0.18
uncontrolled 58 59.2 31 72.1 4 44.4
Eggs controlled 30 37.0 9 25.7 18 52.9 0.06
uncontrolled 51 63.0 26 74.3 16 47.1
Beans controlled 39 43.8 9 36.0 9 25.0 0.14
uncontrolled 50 56.2 16 64.0 27 75.0
Milk and dairy products controlled 18 36.0 16 43.2 23 36.5 0.75
uncontrolled 32 64 21 56.8 40 63.5

Vegetables and fruits

Vegetables controlled 15 25.4 19 46.3 23 46 0.03*
uncontrolled 44 74.6 22 54 27 54
Fruits controlled 34 38.6 8 29.6 15 42.9 0.55
uncontrolled 54 61.4 19 70.4 20 57.1
 NUTRITIONAL NEUROSCIENCE 7

Table 7. Logistic regression analysis for significant nutritional recommended, respectively), while fat intake was opti-
predictors of uncontrolled seizures in epileptic patients among mum to recommended levels. This signifies that these
the study population (n = 150). patients had a high carbohydrate-to-fat ratio. This dis-
Odds 95% CI
turbed ratio could lead to improper seizure control,
Variables B P-value ratio Lower Upper
but, unfortunately, no statistically significant difference
Vegetable intake
Vegetable intake 0–2 .852 .049 2.35 1.003 5.485 was found between controlled and uncontrolled patients
times/week regarding the mean and median of macronutrient daily
Vegetable intake 3–4 −.058 .897 .95 .393 2.269
times/week intake. This was in accordance with a Brazilian study
carried out by de Azevedo Fernandez et al. [2] who
Calories intake
Calories intake (< 75% −.905 .073 .41 .150 1.090 found elevated carbohydrate and protein intake in
from RDA) people with epilepsy (approximately 2 and 4 times
Calories intake (75% – −.274 .609 .76 .266 2.176
< 100% from RDA) higher than recommended, respectively). Contrary to
Calories intake (100% – −1.614 .003 .20 .070 .569 our results, they found that the daily intake of monoun-
< 120% from RDA)
Constant .895 .043 2.448 saturated and polyunsaturated fatty acids, such as
Note: R-square = 0.16, RDA: recommended dietary allowance; CI: confidence omega 3 and 6, was below recommended levels, whereas
interval. saturated fatty acid intake was significantly higher than
recommended guidelines. In agreement with our
Four (33.3%) patients with controlled seizures prac- results, they did not find significant differences in food
ticed sports whereas, 8 (66.7%) patients with uncon- intake between patients with controlled versus uncon-
trolled seizures practiced sports. trolled seizures.
There was no statistically significant difference In the present study, a statistically significant difference
between patients with controlled versus uncontrolled was detected regarding adequacy of caloric intake between
seizures regarding sports frequency per week (P = 0.7). patients with controlled versus uncontrolled seizures. Sev-
enty-seven percent of patients with uncontrolled seizures
3.3. Regression analysis of nutritional predictors experienced over-caloric intake compared to only 23.1%
of uncontrolled seizures among the study of patients with controlled seizures. However, we did
population not find a statistically significant difference between
carbohydrate, protein, fat, and fiber intake between the
Stepwise logistic regression was performed using the two groups. Moreover, stepwise logistic regression
following variables: frequency of vegetable intake revealed that patients with optimal caloric intake are
per week and percent of caloric intake from the 80% less likely to be uncontrolled than those with over-
RDA. It indicated that those with low intake of veg- caloric intake. This was supported by a study conducted
etables, from 0 to 2 per week, had a 2.3 times higher by Greene et al. [16] who proved that caloric restriction
likelihood of uncontrolled seizure occurrence com- (CR) was an effective dietary therapy for preventing sei-
pared to those with a high intake of vegetables, 5 zures in a genetic model of idiopathic epilepsy. They
times or more per week. Also, those with optimal found that the antiepileptogenic effect of CR was signifi-
caloric intake (100–<120% of RDA) were 80% less cantly correlated with reductions in plasma glucose levels
likely to have uncontrolled seizures than those with and with elevations in plasma ketone body levels. CR
too much caloric intake (120% and more of RDA) reduces energy production through glycolysis. It limits
(Table 7). the ability of the neuron to achieve the high levels of
synaptic activity required for seizure generation. More-
over, it leads to adenosine triphosphate (ATP) release
4. Discussion
through pannexin hemichannels localized in neurons,
Anecdotal reports have proposed that certain foods which would be rapidly degraded to adenosine by ectonu-
might influence the occurrence of seizures. However, cleotidases. The increased level of adenosine activates A1
the existing data are scanty and sometimes controversial receptors, which activate ATP-sensitive potassium
[14]. (KATP) channels. These channels hyperpolarize neuronal
There are conflicting data regarding whether membranes [17].
decreases or increases in bioenergetic substrates are Our study participants had a low intake of minerals,
favorable for seizure control [15]. Our study partici- in particular calcium, Mg, zinc, and potassium. This was
pants had unbalanced macronutrient intake character- in accordance with Bertoli and colleagues [18], who
ized by over-intake of carbohydrates and proteins found that there was a low intake of calcium, iron,
(approximately 1 and 0.3 times higher than and zinc in children with refractory epilepsy. Prior
8 R. S. ISMAIL ET AL.
reports have suggested that altered levels of minerals
play an important role in the pathophysiology of sei-
zures [19]. Yuen and Sander [20] found that people
with epilepsy have lower Mg levels than people without
epilepsy. In another study by Oladipo et al. [21] the
plasma Mg concentrations were found to be signifi-
cantly lower in those with epilepsy than in controls.
Mg is important in the utilization of vitamin B6,
which is a cofactor required for gamma aminobutyric
acid (GABA) synthesis. Mg could also inhibit N-
methyl-D-aspartate (NMDA) receptors [22]. Moreover,
significantly lower levels of serum zinc have been
detected in people with epilepsy [19, 23, 24]. Zinc may
play a role in pyridoxal phosphate-mediated regulation
of glutamic acid decarboxylase, the key enzyme in the
synthesis of GABA [25]. Low levels of serum zinc can
induce epileptic seizures by activating NMDA receptors
[26]. Furthermore, Prassad et al. [27] found low levels of
serum calcium in patients with genetic generalized epi-
lepsy when compared to the control group. Also, in a
prospective case-control study conducted by Oladipo
et al. [28] calcium levels were found to be lower in
patients with epilepsy. It was suggested that decreased
serum calcium levels produce a membrane state of
hyper excitability of neurons, which is associated
strongly with seizures.
Several studies have evaluated oxidative stress and
antioxidant status in people with epilepsy. Most of
these studies have shown enhanced levels of oxidative
stress and reduced levels of antioxidant vitamins [29].
This was shown by Gaby [30], who found that vitamin
C increases the latency to first seizure and decreases
the mortality rate and lipid peroxidation levels in
adult rats with seizures induced by pilocarpine. Also,
Tamai et al. [31] found that plasma vitamin E concen-
trations were lower in children with epilepsy than in
healthy controls. In the current work, we found that
some vitamins (A, C, E, B1, B6, B12, folate and niacin)
were also below the RDA for age and gender. This was
in agreement with Bertoli and colleagues [18], who sta-
ted that mean daily intake of riboflavin and niacin in
children with refractory epilepsy was greatly reduced
compared with European RDA for sex and age.
An imbalance in oxidants and antioxidants is
known to be involved in the pathogenesis of various dis-
eases including epilepsy. Consequently, antioxidant
therapies are important for the treatment of epilepsy
[32]. In the present work, controlled patients have
increased frequency of vegetable intake compared to
uncontrolled patients. Using stepwise logistic
regression, we found that patients with low intake of
vegetables were 2.3 times more likely to be uncontrolled
for seizure occurrence compared to those with a high
intake of vegetables. The mechanism proposed is that
vegetables are rich in antioxidant vitamins, which
limit the oxidative stress by reacting with reactive oxi-
dants [33].
In conclusion, macro- and micronutrient intake were
unbalanced in patients with epilepsy. Patients with over-
caloric consumption and little vegetable intake were
more likely to have bad seizure control. Therefore,
people with epilepsy may benefit from individual nutri-
tional assessment and dietary alteration, which may
comprise a novel approach to epilepsy treatment.
The strength of this work is that it is the first work to
study nutritional intake in a sample of adult patients
with epilepsy and to clarify the nutritional predictors
of uncontrolled seizures among people with epilepsy.
The limitation of this study was that we did not have
the opportunity to analyze micronutrients in serum.
Another limitation to our study is the lack of further
categorization of fat dietary intake data into saturated
fat, trans fat, monounsaturated fatty acids, polyunsatu-
rated fatty acids and omega-3 fatty acids.
Conflict of interest
The authors declare that the research was conducted in
absence of any commercial relationships that could be
constructed as a potential conflict of interest.
Availability of data and material
The datasets generated and/or analyzed during the cur-
rent study are not publicly available due to the current
Cairo University regulations and Egyptian legislation
but are available from the corresponding author on
reasonable request and after institutional approval.
Acknowledgement
The authors acknowledge subjects for their participation and
cooperation in this study.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Notes on contributors
Rania Shehata Ismail is currently an associate professor of
Neurology at Cairo University (since 2019). I am interested
in epilepsy, multiple sclerosis, and movement disorders sub-
specialties, and medical teaching programs. I have multiple
international publications in epilepsy, Parkinson’s disease
and multiple Sclerosis. I am a member of the American

Academy of Neurology and Egyptian society of Neurology. I
am one of the staff members of Cairo University Epilepsy
Unit.
Nirmeen A. Kishk is currently a full Professor of Neurology at
Cairo University (since 2014). After completing his residency
training at the Neurology department Cairo university hospi-
tals, she has multiple fields of interest. She focused on epilepsy
clinic science 2004 after that at 2010 she became the modera-
tor of the Epilepsy clinic and share in the upgrading into Epi-
lepsy Unit; she joined many internationally educational EEG
& Epilepsy courses and schools. She is Vice Secretary-General
of the Egyptian Society Against Epilepsy (ESAE), Chapter of
the International League Against Epilepsy (ILAE), and Join
ILAE COVID Task Force as a representative Eastern Mediter-
ranean. She is the principal investigator for ongoing national
researches in her university focused on drug-resistant
Epilepsy.
Hoda Ibrahim Rizk is currently an associate Professor of Pub-
lic Health and Community Medicine at Faculty of Medicine,
Cairo University (since 2016). She teaches different theoretical
and practical topics of Public Health and Community Medi-
cine for both undergraduates and post graduate medical stu-
dents. She focused on Biostatistics & research Methodology,
basic &clinical nutrition, health system research and quality.
She has many publications on nutrition, health care services
and quality.
Thanaa El-Kholy, is currently Professor of Nutrition and
Food Science, Faculty of Home Economics, Al-Azhar Univer-
sity, Tanta. She has multiple fields of interest as nutrition,
therapeutic nutrition, nutrition during different age stages,
and food sciences.
Lamiaa M Abd El-Maoula, is currently lecturer of Nutrition
and Food Science, Faculty of Home Economics, Al-Azhar
University, Tanta. She has multiple fields of interest as nutri-
tion, therapeutic nutrition, nutrition during different age
stages, and food sciences.
Ola Ibrahim El-Desoky, is currently lecturer of Nutrition and
Food Science, Faculty of Home Economics, Al-Azhar Univer-
sity, Tanta. She has multiple fields of interest as nutrition,
therapeutic nutrition, nutrition during different age stages,
and food sciences.
Shaimaa Shaheen, is currently lecturer of Neurology at Cairo
University. She is interested in epilepsy and demetia subspe-
cialties. She has multiple international publications in differ-
ent neurological subspecialties. She is one of the staff
members of Cairo University Epilepsy Unit.
Enji El-Sawy, is currently lecturer of Neurology at Cairo Uni-
versity. She is interested in epilepsy and dementia subspecial-
ties. She is one of the staff members of Cairo University
Epilepsy Unit.
Author contributions
Rania Shehata Ismail, Nirmeen Adel Kishk, Hoda Ibra-
him: research idea, data acquisition, data analysis and
interpretation, and manuscript writing and reviewing,
Thanaa El-Kholy, Lamia Abd El-Maoula, Ola Ibrahim
El-Desoky: data acquisition, data analysis and
NUTRITIONAL NEUROSCIENCE 9
interpretation, Shaimaa Shaheen, Enji El-Sawy: data
interpretation and manuscript writing and reviewing.
ORCID
Nirmeen Adel Kishk http://orcid.org/0000-0003-4410-7814
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