Nutritional status, nutrient imbalances, food-related behaviors and dietary supplements use among patients with celiac disease on a gluten free diet in Lebanon: a national cross-sectional study

Introduction

Celiac disease (CD) is a chronic inflammatory autoimmune disorder characterized by partial to total villous atrophy of the small bowel.¹ The exposure to dietary wheat gluten and proteins of rye and barley triggers CD among genetically predisposed persons.² In certain circumstances, individuals show no symptoms and the diagnosis is only possible through serologic screening.³ According to the European Society for the Study of Celiac Disease (ESsCD) guideline, the diagnostic criteria depend upon the exposure to dietary gluten or related proteins of rye and barley-dependent symptoms, through some histopathologic findings (villous atrophy and crypt hyperplasia) from a biopsy of the duodenum, specific antibody levels, HLA-DQ2 and/or HLA-DQ8.⁴ The prevalence of CD is estimated to be one to two individuals per 100 worldwide⁵ and roughly one in 99 among children and adolescents.⁶ Moreover, according to a recent systematic review and meta-analysis, the pooled seroprevalence of CD in the general population is significantly higher in children (2%) compared with adults (1%, p-value=0.01) and significantly greater among females (1.65%) compared to males (0.8%, p-value=0.04).⁷ The pooled sero-prevalence of CD in the Middle Eastern area (1.47%) is higher than that in South Asia (1.25%) and East-Asia (0.06%).⁷ The highest prevalence among the Arab regions was reported in Saudi Arabia (3.2%), and the lowest in Tunisia (0.1%).⁸ In Lebanon, the prevalence of CD was around 0.5% in 2011.⁹ Furthermore, women have shown elevated prevalence compared to men in the Arab countries⁸ and according to solid evidence, the risk becomes common and high if a first- or second-degree relative has been previously diagnosed.⁶

CD affects the proximal part of the small intestine, which in turn results in micronutrient malabsorption, particularly iron, folic acid, vitamin B12, calcium and vitamin D, resulting in anemia on the short term and reduced bone density on the long-term.² Further, beyond inflammation and malabsorption, CD is characterized by recurrent abdominal pain, nausea, vomiting, steatorrhea and loss of weight which also compromise the nutrition status of affected individuals.⁶ Until today the only therapy for individuals with CD remains the adherence to a gluten-free diet (GFD) along with the avoidance of foods containing wheat, rye, and barley derivatives.¹⁰ According to several studies, the adherence to a strict GFD can reduce the risk of health-related complications, for instance: malignancy, osteoporosis, growth retardation in children, liver disorders and reproductive tract disorders.¹ According to recent data, the adherence to GFD has remained unchanged over the past twenty years^11,12 and a considerable number of individuals with CD do not adhere to the dietary restrictions, which affects the patient’s quality of life and causes compromised nutrition status.¹⁰ Moreover, some individuals with CD may look for other approaches to treatments such as complementary and alternative medicine (CAM) which include dietary supplements (DS) use.¹³ There is scarce data on the DS use in CD. Many studies identified the DS use among CD patients to be within a range of 21.6% to 23.6%.¹³ This percentage was less than the percentage of DS use among the general population (27%).¹³ Thus, investigating the nutrition status through dietary assessment of individuals with CD is warranted especially among children, adolescents, and adults who followed a GFD to avoid malnutrition and related morbidity. Such an evaluation of GFD adherence should be executed by experienced trained dietitians; however, the access to such dietitians with expertise in the field of CD may be limited. Beyond GFD adherence, many reasons exist for the necessity of nutritional investigation including the poor public awareness about CD, and the lack of regulations for the production and analysis of gluten-free labelled products.¹⁴ To the best of our knowledge, there are no published data that address the nutrition situation and dietary supplements use among individuals with CD who followed a GFD in Lebanon. Therefore, the aim of the present study was to assess the nutritional status, food-related behaviors, caloric, macro- and micronutrients intake and dietary supplements use among Lebanese individuals with CD who followed a GFD.

Methods

Results

A total of 50 participants (78% females; mean age=31.74 ± 15.64 years) was enrolled in the present study between February and July 2018. Out of 50, eight participants were aged below 18 years. Age categories were classified according to the dietary reference intake classes²⁷ of which 46% of the population’s age ranged between 31 and 50 years. In the current study, females were younger than males (p-value=0.03). Moreover, around 66% of all the participants had university degrees and more than 70% were remunerated for more than 1,500 million Lebanese pounds (LBP) per months. Half the study’s participants were married. Overall, in almost all the characteristics, there were no significant differences between females and males in this study (p>0.05). The sociodemographic characteristics of the study participants are displayed in Table 1.

Table 2 includes the medical history, anthropometric measures and lifestyle characteristics of the study participants. In the current study, males were taller than females (p-value=0.042). It was observed that the weight of all participants increased in a range of 4 to 5.6 kg since being diagnosed with CD. This was significantly higher among males compared to females (p-value=0.023). Moreover, 45% of females were overweight compared to 37% males. The assessment of malnutrition was based on Kotze et al.²⁵; a weight loss of 10% to 30% indicating mild to moderate malnutrition were shown in 14% of the study population. The body composition analysis conducted for the study participants revealed that 40% of them had low muscle mass (5.0 to 32.8% for males and 5.0 to 25.8% for females).²⁸ Further, the mean muscle mass was higher in males compared to females (p-value=0.034). In total, 60% of participants were having high fat mass (more than 20% in males and more than 30% in females). In addition, the mean value of fat mass among women where higher than that among men (p-value=0.014). Furthermore, the majority of the study participants had low visceral fat and there were no significant differences regarding the mean and SD of visceral fat among both genders (p-value=0.25).

As for the medical history, around half the study participants had a family history of CD. The mean age at diagnosis was 22.28±13.55 (range=1-57 years). Symptoms related to CD such as abdominal bloating, diarrhea, headache, and flatulence appeared in most participants (94%) and 6% were asymptomatic. Around 66% were facing moderate to severe symptoms. According to the medical history, other comorbidities along with CD were reported. Around 24% of participants had CD with other diseases of which dermatitis, arthritis, lactose intolerance and food allergy. As for the medications, 78% of the study participants reported were on medical treatments for CD symptoms.

As for the laboratory values, hypoalbuminemia was observed in 14% of the study population. Women were having significantly higher mean and SD levels of albumin compared to men (p-value=0.02). Out of 50 participants, 38% and 16% were presenting low serum levels of iron and vitamin B12, respectively. None of the study participants presented with folate deficiency. As for the lifestyle behaviors, the majority of participants were non-smokers, non-drinkers and physically inactive (Table 2).

The food-related behaviors assessed among the study participants are presented in Table 3. Around 80% of the study participants reported reading nutrition labels when shopping groceries. Moreover, almost 96% of them were following a nutritional diet of which was the GFD. To assess their adherence to GFD, the examination of 96% of the participant’s three-day records reported low intake of gluten (<3g per day). Only 4% weren’t adhering to the GFD recommendations. As reported by the participants, some barriers including family ignorance (among 6% of the population), language on the nutrition labels (among 20% of the population) and expensive GF products (among 78% of the population) were limiting the adherence to GFD. It was observed that 72% of the study population had good cooking experience and 64% of the study participants were involved in preparing meals for themselves. On the other hand, almost all the subjects were unaware of a possible cross-contamination during cooking. Despite that, 82% of the subjects with CD preferred fast foods, although they consumed their meals frequently at home (92%). It was reported that the adherence to GFD by these participants induced a hunger feeling during the day. Most of our study population necessitated extra care by family members regarding cooking and eating. No significant differences were observed between genders.

Energy and protein intake compared to the recommended daily allowances (RDA)

Table 4 shows the mean energy and nutrients intake calculated through the three-day food records reported by the study participants or their families. Among female children aged four to eight years, the mean daily energy (E) and protein (P) intake were estimated as 1396 ±424.15 Kcal/d and 56.41 ±18.31 g/d, respectively. In comparison with the reference values of the recommended daily allowances (RDA), the daily intake of E and P was 130% and 268%, respectively. On the other hand, it was observed that female children aged 9-13 years had insufficient daily E intake (75% vs RDA) but surpassed by 317% the daily protein requirements. Similarly, among the female participant’s age groups 19-30, 31-50 and 50-70, there were inadequacies in the daily E intake along with overconsumption of protein per day. Otherwise, inadequacies in the daily E and P intake were observed among the male children (four to eight years) and those aged 19 to 30 years. Moreover, among those aged 9-13 and 31-50, the daily E intake was inadequate, but the P intake was high. No significant differences regarding the daily E and P intakes were observed between females and males, except in the 19-30 age group, where the daily energetic and protein ratios were high in females compared to males (p-value=0.024 and p=0.047, respectively).

Table 4. Energy and protein intake and their reference values according to recommended daily allowance (RDA) among the study population.

EI: energy intake; PI: protein intake.

Variables	Overall	Female	RDA	% of adequacy	Male	RDA	% of adequacy	p-value (F vs M)
4-8
EI (kCal)	1396±424.15	1564±88.6	1200	130	1060±483	1400	75	0.195
PI (g)	56.41±18.31	51.22±9.8	19	268	14.14±10	19	74	0.384
9-13
EI (kCal)	1202.5± 272.2	1010±0.0	1600	75	1395±0.0	1800	77.5	-*
PI (g)	39.85±39.85	108.36	34	317	52.00	34	152	-*
19-30
EI (kCal)	1564±177.26	2076.25±39.7	2200	94	1530± 255.2	2900	52.7	0.024
PI (g)	76.84±35.4	84.97± 8.86	46	184	92.7±12.92	56	60	0.047
31-50
EI (kCal)	1758.3±772.4	1669.85±177.1	2200	76	2348±26.1	2400	98	0.942
PI (g)	178±35.43	71.99±9.702	46	156	84.73±11.5	56	151.8	0.423
50-70
EI (kCal)	1701.08±296	1701.08±296	1900	89.5	-*	2300	-	-*
PI (g)	81.183±33	81.183±33	46	176	-*	56	-	-*

* The analysis couldn’t be generated due to the low sample size; the missing values in the table are due to the absence of males above the age of 50 years.

The average daily nutrient intake of calcium, iron and vitamin D is reported in Table 5. Among females and males, none of the study participants showed adherence to the daily recommendations for calcium and vitamin D intake. On the other hand, almost all the study participants from both genders showed a high daily consumption of iron.

Table 5. Average daily nutrient intake of subjects and percentage of adequacy according to recommended daily allowance (RDA).

Nutrient intake/Age	Mean of overall population	Female			Male			P-value (F vs M)
		Actual intake	RDA29	% Adequacy	Actual intake	RDA29	% Adequacy
Calcium (mg/day)a,b
4-8	702.41±118.07	768.63±173.75	1000	77%	569.98±41.02	1000	57%	0.98
19-30	540.16±325.47	601.92±404.41	1000	60%	453.96±173.13	1000	45%	0.46
31-50	536.34±287.18	547.36±306.84	1000	55%	462.91±58.55	1000	46%	0.64
51-70	454.78±190.89	454.78±190.89	1200	38%	-	-	-	-
Iron (mg/day)a,b
4-8	16.303±3.11	22.48±7.48	10	194%	15.17±4.72	10	101%	0.09
19-30	30.80±5.55	33.49±6.39	18	158%	27.03±10.56	8	338%	0.59
31-50	17.22±3.95	17.58±4.49	18	98%	14.79±6.37	8	185%	0.81
51-70	18.81±7.56	18.81±7.56	8	235%	-	8	-	-
Vitamin D (ug/day)a,b
4-8	6.54±2.21	8.56±2.87	15	57%	2.52±0.06	15	17%	0.003
19-30	10.42±4.93	8.48±2.91	15	57%	13.12±11.82	15	88%	0.66
31-50	3.56±0.89	3.94±1.00	15	26%	1.00±0.39	15	7%	0.28
51-70	2.28±0.62	2.28±0.62	15	15%	-	-	-	-

a In each age category, the age groups (13-14) were removed due to the limited number of patients.

b The missing values in the table are due to the absence of males above the age of 50 years.

Dietary supplements were used by 54% of the study population of which 38%, 10%, 46%, 18%, 16% and 4% used vitamin D, vitamin B12, iron, calcium, folate and probiotics, respectively. No difference was observed between genders regarding DS use (Table 6). According to Figure 1, it appears that the usage of DS among individuals with CD was not excessive.

Table 6. Supplements intake among study participants, by age group, by gender and reference to recommended daily allowance RDA for each element.

	Overall (N=50) N (%)	F (N=39;78%) N (%)	M (N=11; 22%) N (%)	P-value
Dietary supplements use				0.108
No	23 (46)	16 (41)	7 (63.6)
Yes	27 (54)	23 (59)	4 (36.4)
Vitamin D				0.125
No	31 (62)	22 (56.4)	9 (81.8)
Yes	19 (38)	17 (43.6)	2 (18.2)
Vitamin B12				0.909
No	45 (90)	35 (89.7)	10 (90.9)
Yes	5 (10)	4 (10.3)	1 (9.09)
Iron				0.158
No	27 (54)	19 (48.7)	8 (72.2)
Yes	23 (46)	20 (51.3)	3 (27.8)
Calcium				0.384
No	41 (82)	31 (79.4)	10 (90.9)
Yes	9 (18)	8 (20.6)	1 (9.09)
Folate				0.261
No	42 (84)	31 (81.5)	11 (100)
Yes	7 (16)	7 (18.5)	0
Probiotics				0.443
No	48 (96)	37 (94.8)	11 (22)
Yes	2 (4)	2 (5.2)	0

Figure 1. Dietary supplements use and type among study participants.

Discussion

This study, the first of its kind in Lebanon, highlights the nutrition imbalances, protein-energy malnutrition, adherence to GFD, food-related behaviors and dietary supplements use among participants with CD. Our findings show that 78% of individuals with CD were women. This finding was higher than the data reported by Jansson-Knodell et al.,³⁰ and Ashtari et al.⁷ which showed that the prevalence of women diagnosed with CD was 65% between 1990 and 2015 and the sero-prevalence of CD reported among women was 165 women out of 2000, respectively. On the other hand, our finding aligned the data reported by Singh et al. which showed that the prevalence of CD was higher among women compared to men.³¹ In addition, according to Bai et al., there are physiological differentials among genders in CD³²: “men have indirect evidence of greater malabsorption than females and have female-predominant associated diseases when they present with celiac disease”.³² This study supported our finding concerning the remarked protein-energy deficiency among males compared to females in our study. Further, almost all the participants had symptoms related to CD such as abdominal bloating, diarrhea, headache, and flatulence; around 66% were facing moderate to severe symptoms and 78% of them reported being on a medical treatment for CD symptoms. These findings were two times higher than the prevalence reported by Stasi et al., who showed that 22% of individuals with CD faced persistent abdominal symptoms.³³ In the present study, 14% presented hypoalbuminemia and mild to moderate malnutrition (10%-30% weight loss in the previous six months). This data agreed with Wierdsma et al.³⁴ where 17% of individuals with CD were malnourished (>10% undesired weight loss). In general, patients with CD are misdiagnosed as malnourished and also their malnutrition is always underreported. Thus, physicians tend to ignore mild to moderate weight losses. This can aggravate the nutrition status of these patients and decrease their immunity. On the other hand, the percentage of underweight women (5%) in our study wasn’t in accordance with Wierdsma et al.³⁴ in which 22% of the women were underweight and 29% of the patients were overweight (BMI > 25 kg/m²). Our study showed that around 40% of individuals with CD had low muscle mass and 60% had high fat mass. This might be due to the low physical activity level and unhealthy food patterns. Also, some of the medications ingested by the patients with CD can induce insulin resistance and promote overweightness. This result was in contradiction with the results reported in a national study which showed that subjects with CD had a lower fat mass (17.8±2.0 kg)³⁵ but in concordance with two recent systematic reviews on children and adults that showed that after one year follow-up to GFD’ adherence, fat mass of CD patients significantly increased compared to that at baseline.^36,37 According to Agarwal et al., patients with CD are more susceptible to develop metabolic syndromes and fatty liver diseases.³⁸ Thus, these patients should be regularly counseled by experienced dietitians for nutritional and metabolic factors about healthy diets and physical activity. However, the majority of participants in our study were physically inactive (72%). This prevalence of sedentary patterns among our study population was higher than that reported by Nestares et al. (37%) among children and adolescents³⁹ but lower than the prevalence of physical activity among women with CD in Poland (70%).⁴⁰

Out of 50 participants, 38% and 16% were presenting low serum levels of iron and vitamin B12, respectively. None of the study participants presented folate deficiency. These results showed consistency with a recent systematic review that showed high occurrence of anemia among individuals with CD.⁴¹ Furthermore, micronutrient deficiencies are common features among individuals with CD. This was demonstrated in the study of Bledsoe et al.¹⁹ where weight loss was seen in 25.2%, albumin was low in 19.7%, vitamin B₁₂ was low in 5.3% and folate was low in 3.6% of cases. Moreover, it was shown that 87% of patients with CD in the study of Wierdsma, et al.³⁴ had low vitamin B₆ (14.5%), folic acid (20%), and vitamin B₁₂ (19%). Additionally, 46% of patients with CD had low serum iron, and 32% had anemia.³⁴ This might be due to the lack of knowledge on the importance of micronutrients intake among patients with CD and also due to abdominal distress symptoms that are common in these patients.

In our study, around 80% of participants read nutrition labels when shopping groceries. Reading and understanding food label’s topics have been discussed widely and have been associated with strict GFD adherence.⁴² Our finding was in accordance with Butterworth et al., who showed that amongst 74% of individuals with CD, some factors were in compliance with adherence to GFD: being a member of a celiac society, understanding food label’s language, and having access to gluten-free products with reasonable prices, regular dietetic and medical follow-up.⁴³ Causes of adherence/non-adherence to a GFD are multifactorial and differed according to their nature and magnitude.^44–47 These factors are very correlated with the education level, the economic situation and the readiness of patients to adhere to this diet.^46,47

Almost 96% of our population were following a GFD. To assess their adherence to GFD, the examination of the participant’s three-day records reported low intake of gluten (<3g per day) among 96% of the study participants. Only 4% weren’t adhering to the GFD recommendations. This finding was consistent with a study conducted in individuals with CD in Spain (92.5%).⁴⁸ According to a Spanish study, 72% of individuals with CD showed acceptable adherence which was associated with higher levels of self-efficacy.⁴⁹ Three studies from the UK showed that white patients were adhering to GFD in a range from 53 to 81%.⁵⁰ Non-adherence to GFD was also associated with diagnosis at younger ages and smoking.⁵⁰ This was not shown in our study. In Canada, GFD adherence was assessed and revealed that the percentage of strict adherence was only 56%.⁵¹ The assessment of GFD adherence of 70 Swedish adolescents with CD showed that 86% of them were adherent to GFD five years after screening.⁵² Moreover, of 5310 adult and adolescent Australians and New Zealanders with CD, 61% ashered to a GFD.⁵³ Three studies on adolescents from Brazil identified adherence rates from 36 to 86% taking into consideration that younger children (up to 12 years) were more likely to comply with the diet⁵⁴ while teenagers interrupted their diet purposefully. Parents of pediatric patients with CD from the Slovak Republic, reported a GFD adherence of 69% by children.⁵⁵ In addition, among 38 studies, the adherence was ranging from 42 and 91%.⁴⁹ According to a recent systematic review of 49 studies, the adherence rates were ranging from 23 to 98%.⁵⁶ This wide variability in adherence rates may be explained by the different populations examined (e.g., adults, adolescents, children, ethnic minorities), but also by the different tools used for evaluating adherence.

As reported by the participants, some barriers including family ignorance (among 6% of the population), language on the nutrition labels (among 20% of the population) and expensive GF products (among 78% of the population) were limiting the adherence to GFD. These findings were in concordance with Muhammad et al.,⁴⁴ who showed that not understanding food labelling was associated with lower GF dietary adherence scores. A higher proportion of individuals in the United Kingdom (UK) reported difficulties in acquiring knowledge about GF products (ranging between 5% and 76%) and understanding of food labels (4%-53%).⁵⁷ It was observed that 72% of the study population had good cooking experience and 64% of the study participants prepared their meals. On the other hand, almost all the subjects were unaware of a possible cross-contamination during cooking food. Despite 82% of the subjects with CD preferring fast foods, they frequently consumed their meals at home (92%). Beyond cooking meals at home and cross-contamination, our findings were consistent with the findings reported in a recent systematic review indicating that the most significant barriers limiting the adherence to GFD included: “lower knowledge of CD” (35%); “restaurant/supermarket shopping” (30%); “poor patient education from practitioner” (17.5%); and “low intention/motivation to adhere to a GFD (17.5%)”.⁴⁵

In our study, patients with CD had an inadequate total daily energy intake. This finding was concordant with several studies from Poland, Germany and Spain.^58–60 As for nutrients intake, among females and males, none of the study participants showed adequacy to the daily recommendations for calcium and vitamin D intake. These results, altogether, showed an unbalanced diet in terms of micronutrients, that were in accordance with those shown in several studies.^14,61–63 On the other hand, almost all the study participants from both genders showed a high daily consumption of iron. This finding contradicts the results reported in other studies.^60,64–66 In general, patients with CD are always alarmed by their physicians concerning anemia. Thus, these patients tend to consume more food sources of iron and ignore other nutrients.

As for dietary supplement use, it appears that the usage of DS among individuals with CD wasn’t in excess of that reported in the general population in Lebanon.⁶⁷ In our study, the most commonly used DS was vitamin D and the least used one was probiotics. Despite that most patients with CD are at risk of micronutrient deficiencies, however, the lack of knowledge concerning dietary supplement use is one of the challenges related to malnutrition among these patients.⁶⁸ This can explain the occurrence and persistence of gastrointestinal manifestations among the majority of participants in the current study.

Conclusion

Monitoring nutritional status using dietary, anthropometric, blood tests and assessing physical activity are the key components in the management of CD. The ideal GFD should be balanced with macronutrients and micronutrients, with reasonable access and prices. Fortification/enrichment of GF foods that are frequently consumed should be encouraged to avoid deficiencies. This underlines the critical role of dietitians in education and maintenance of healthy GFD among individuals with CD.

Data availability