Neurology India, Vol. 58, No. 2, March-April, 2010, pp. 209-212
Prevalence of low dietary calcium intake in patients with epilepsy: A study from South India
Bindu Menon1, Chittari Venkata Harinarayan2, Marella Neelima Raj2, Swapna Vemuri2, G Himabindu2, TK Afsana2
1 Department of Neurology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Andhra Pradesh, India
Correspondence Address: Bindu Menon, Department of Neurology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Andhra Pradesh, India, email@example.com
Date of Acceptance: 06-Oct-2010
Code Number: ni10057
Background: The effects of antiepileptic drugs (AED) on bone health are well documented. Inadequate dietary intake of calcium and vitamin D plays a vital role and further compromises the bone health.
Keywords: Diet, calcium, epilepsy
Calcium and vitamin D are essential for the proper development of the bone and skeletal system. Vitamin D is a fat soluble vitamin synthesized by the body from the exposure to ultraviolet (UV) rays from the sun, while calcium is obtained through diet. The other source of vitamin D is fortified food. In most developed countries, milk is fortified with calcium, but it is yet to be followed in India. Bone is a dynamic tissue which is in a state of constant remodeling. When hypocalcemia starts setting in, calcium from the bone is mobilized to maintain normal serum calcium eventually making the bones weaker. There is growing awareness of effect of antiepileptic drugs (AED) on bone health in people with epilepsy (PWE). Long-term antiepileptic therapy can lead to a reduction in bone mineral density.  Since the initial reports of adverse effects of AED on bone four decades ago,  there has been increasing understanding of the mechanism of AED induced bone loss. ,,, The effects of AED on bone health can be confounded in a situation of low dietary calcium intake. To the best of our knowledge, there has been no study documenting the details of diet in PWE with special reference to calcium and related minerals in India. We conducted the dietary survey in PWE on AED with special reference to bone health.
Materials and Methods
The study was conducted in a tertiary-care hospital located in southern Andhra Pradesh, (lat 13.4° N, long 79.2° E) a province in south India. The average cloud free sunshine per day is 8-10 hrs through out the year with the solar zenith angle of 9.92° in summer and 38.2° in winter. The UV index at this latitude is 7-12. There is little variation in the peak intensity of sunlight and little seasonal variation. The staple diet of the region is predominantly rice.
Patients with epilepsy on AED treatment attending the outpatient department, who were physically active, were included in the study. Patients with comorbid illness, such as, gastrointestinal illness and chronic liver and kidney diseases were not included in the study. None of the patients were on any supplementation tablets of calcium or vitamin D. The duration of AED treatment and the medication history was recorded. The diet history was collected by recalling the diet consumed in the past 5-7 days. The documentation of dietary pattern was by a single observer. The validity and repeatability of the documentation was rechecked at random by one of the authors over and no significant error in the documentation of dietary history was noted. From the raw weights, the total energy, carbohydrate, proteins, fat, calcium, phosphorous, and phytate intakes were calculated using a published food composition table, detailing the nutritive value of Indian foods.  As phytates interfere with the absorption of calcium, phytate calcium ratio was calculated. The major percentage of food in a day comprising the calcium, phytate, phosphorus, proteins, and fat was analyzed. The analysis was done for the total cohort and for the individual age and gender groups. The groups based on age of the patients were: Group I: < 14 yrs; Group II: 14-20 yrs; Group III: 21-45 yrs; and Group IV: > 46 yrs.
Descriptive results are presented as mean ± SD. Student′s t-test was used to compare the differences between the various groups. Pearson′s coefficient was calculated for the correlation. P values < 0.05 were considered significant. Statistical analysis of the data was also performed using a two-way ANOVA calculation with Turkey′s pair wise comparisons between groups. Analyses were performed using statistical package SPSS version 11.5.
A total of 362 patients with a mean age of 29 ± 15 years were recruited for the study. There were 190 females. The mean age for males was 29 ± 15 years and 28 ± 14 years for females. Sixty percent of the patients were from low socioeconomic group and 40% from middle income group. The distribution and mean age in each group were: Group I: n = 46, 11 ± 3 yrs; ,Group II: n = 80, 17 ± 2 yrs; Group III: n = 181, 31 ± 7 yrs; Group IV: n = 55, 56 ± 8 yrs. Mean duration of treatment was 4 ± 3 yrs. The prescribed AED′s were: phenytoin (31%), phenobarbitone (6%), carbamazepine (15%), sodium valproate (8%), clobazam (4%) while 36% were on polytherapy.
The diet of the total cohort comprised 2,007 ± 211 Kcal/day, carbohydrate 335 ± 33 gm/day; protein 31 ± 7 gm/day; fat 18 ± 2 gm/day; calcium 294 ± 40 mg/day; phosphorus 557 ± 102; phytates 179 ± 30 mg/day; phytate/ calcium ratio 0.56 ± 0.2. Of the total energy intake, carbohydrate contributed to 66%, proteins 6%, fat 8%, milk and milk products 4%, and other sources 16%. The carbohydrates in the diet comprised rice, wheat, and ragi (Eleusine coracana), which was consumed by 81%, 11%, and 8% of the patients. The protein source included pulses and legumes; of which red gram dal was the main pulse consumed by 94%; black gram dal, green gram dal, and horse gram dal was consumed by 4-6% of them. Of the legumes, groundnut was consumed by 95% and peas by 5%. Animal sources of protein were consumed by 89% of the patients on an average of once per week constituting of chicken (53%), mutton (19%), egg (14%), fish (3%). Milk and milk products were consumed by 42%, which comprised milk, buttermilk, curd, and ghee. Rest of the patients did not consume any milk products. Diet comprising of beans, brinjal, lady′s finger, carrot, bitter gourd, drumsticks, cabbage, beetroot, and cucumber formed the vegetable source in the diet which was consumed by 96% of the patients.
The daily total calories intake of males (2072 ± 206) Kcal/day was significantly higher than females (1948 ± 198) kcal/day (P < 0.001). The daily dietary calcium (301 ± 40 mg/day) of males was significantly higher than females (287 ± 39 mg/day) (P < 0.001). The daily dietary phosphorus (583 ± 104 mg/day), phytate calcium ratio (0.54 ± 0.21), proteins (32.86 ± 7.55 mg/day), fat (18.25 ± 2.30 mg/day) in males was significantly higher than females; dietary phosphorous (534 ± 95 mg/day) (P < 0.001), phytate calcium ratio (0.59 ± 0.20) (P < 0.01), proteins (28.79 ± 6.30 mg/day) (P < 0.001), fat (17.48 ± 2.05 mg/day) (P < 0.001), respectively. There was no difference in the dietary carbohydrate and phytate consumption between males and females.
The dietary pattern of the various age groups is shown in [Table - 1]. There was no difference in the daily dietary calcium intake among different age groups or socioeconomic pattern. The dietary phytate was lower in group II (P > 0.01) and III (P < 0.03) compared to group I. The daily dietary calcium of males was significantly higher than females in group II (males 310 ± 36, females 287 ± 38; P < 0.01) and group III (males 298 ± 41, females 284 ± 38; P < 0.03). Analysis of variance with Turkey′s pair wise comparison showed that the dietary phytates was higher in females in group I compared to III (P < 0.005) and IV (P < 0.032). The other parameters did not show any significance. There was no difference among different age groups in males in any parameters. There was a positive correlation between dietary calcium with total energy (r = 0.578; P < 0.001), dietary phosphorous (r = 0.708; P < 0.001), dietary phytates (r = 0.360; P < 0.001), dietary proteins (r = 0.544, P < 0.001), dietary fat (r = 0.461, P < 0.001); dietary phosphorous showed a positive correlation with dietary calcium (r = 0.708, P < 0.001), dietary proteins (r = 0.679, P < 0.001), dietary fat (r = 0.415, P < 0.001) and total energy (r = 0.442, P < 0.001) and a negative correlation with dietary phytates (r = -0.114, P < 0.001), PC (r = ---0.477, P < 0.001). Dietary phytates showed a positive correlation with phytate calcium ratio (r =0.556, P < 0.001) and a negative correlation with age (r = -0.081, P < 0.05), DP (r = --0.114, P < 0.02).
Nutrition plays a major role in maintaining the bone health. Our study showed that the diet of all patients with epilepsy was deficient in total calories and calcium, this was so across all the socioeconomic groups. The diet of children and adolescent was far below the recommended daily dietary allowance (RDA) of calcium of 400 mg in adult men, women and 1,000 mg pregnant and lactating women by the Indian Council of Medical Research (ICMR).  This is in contrast to 800 to 1,000 mg/day for adult men and women and 1,200 to 1,300 mg/day for pregnant and lactating mothers recommended by the US guidelines.  Low dietary calcium leads to decreased plasma calcium which triggers secondary hyperparathyroidism leading to osteoclast activity and calcium release from bone. With aging, there is reduced intestinal calcium absorption, increased bone resorption than formation. Moreover, the demand of calcium is increased in women in the childbearing age group. Our study showed that women aged between 15-45 yrs were grossly deficient in their dietary calcium intake. The importance of dietary calcium needs to be emphasized in women in preconception period, during pregnancy and during lactation as this affects the health and nutrition of the offspring. Further bone loss is accelerated in postmenopausal women and old age. A healthy bone at an old age depends on the stores of nutrient in the bone in the early childhood and adolescent.  This study showed that the diet in this age group was also deficient in calcium. Similar findings have been reported the earlier study.  There is a two to six times increased risk for fracture in PWE than in the general population.  The risk of fracture could be definitely more in patients with weak bones. In the present study, patients were mostly on first line AED′s either as monotherapy or combination. There is mounting evidence of AED induced bone changes with carbamazepine, ,, phenytoin,  phenobarbitone,  valproate. ,, Low dietary calcium, like in our study group, further accelerates the parathyroid response to vitamin D insufficiency. A study done in the early 70′s in India documented osteomalacia by biochemical and histopathological studies in 71.4% of patients with epilepsy. 
In a setting where the diet of the population is already low in calcium, the effect of AED can further accelerate the bone loss. Moreover, in the present study, only 42% of the patients consumed milk and milk products which is the principal source of dietary calcium. Non dairy sources of food cannot meet the requirement of calcium.  Hence, educating PWE to increase the milk consumption needs to be emphasized during initiating AED treatment. Calcium absorption can be reduced because it binds to fiber, phytate or oxalate in the intestine. Phytate or phytic acid is found in grains, nuts and seeds and can bind with calcium making it less absorbable by forming insoluble complexes and reducing its bioavailability.  This study showed that there was a positive correlation with calcium and phytate intake and the phytate/calcium ratio was high in our patients, which will further hinder the bioavailability of available calcium. Hence, the available calcium in our population may be still lower than the calculated dietary calcium which has been proven in the studies.  The dietary phytates in general was higher in Group I than in the other groups and particularly in females in Group I (< 14 years). There has been conflicting evidence regarding the interaction of protein and calcium in the diet. Recent evidence states that protective effect of calcium for the skeleton is evident only when protein intake is relatively high.  Our patients were very low in their dietary protein intake which could be detrimental to the calcium absorption.
The present study highlights the inadequate dietary calcium intake and the high dietary phytates, which further limit the available calcium. Moreover, in India, majority of patients are on first line AED which affects the bone health. This study highlights that the dietary requirements of calcium of PWE were far below the recommended daily dietary (RDA) allowance by ICMR. The major nutrient source of calcium; milk intake was very low in our study group. High phytates in the diet can further compromise the available calcium, and hence the quality of diet needs to be counseled. Nutrition remains a modifiable aspect of calcium supplementation. As there are no consensus guidelines as to when calcium should be supplemented, it will definitely be worthwhile to enrich the dietary calcium. Calcium-fortified foods and calcium supplements are an option for individuals who cannot meet their calcium needs from foods naturally containing this mineral. Adequate sunlight exposure and physical activity is to be encouraged. There is an urgent need for educational intervention in the population with special reference with PWE so as to improve the quality of the life.
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