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What is the evidence to support the nutritional adequacy of a gluten-free dietary pattern?



Conclusion Statement

For newly diagnosed children and adults with celiac disease, studies report that compliance with a gluten-free dietary pattern results in significant improvements in nutritional laboratory values, such as serum hemoglobin, iron, zinc and calcium, as a result of intestinal healing and improved absorption. However, adherence to the gluten-free dietary pattern may result in a diet that is high in fat and low in carbohydrates and fiber, as well as low in iron, folate, niacin, vitamin B-12, calcium, phosphorus and zinc. A small number of studies in adults show a trend toward weight gain after diagnosis; further research is needed in this area.

Evidence Summary

One neutral-quality randomized controlled trial, four neutral-quality cohort studies, three case-control studies (two positive-quality, one neutral-quality), one neutral-quality longitudinal study and four cross-sectional studies (two positive-quality, two neutral-quality) in children and adults were evaluated to investigate the nutritional adequacy of the gluten-free dietary pattern.

Anthropometric and Laboratory Values

In a neutral-quality randomized controlled trial by Kemppainen et al (1998) in Finland, 34 newly diagnosed patients followed a gluten-free diet for 1 year, with or without oats, in which compliance was measured using 4-day food records and the oat products were analyzed for gluten-content. Anthropometric measurements and nutritional laboratory values did not differ among the 3 atrophy groups with the exception of serum ferritin (P < 0.05) and erythrocyte folate (P < 0.05), which were lower in patients with total villous atrophy than in the other groups. Most of the abnormal biochemical values were normalized during 1 year of gluten-free diet.

In a neutral-quality cohort study in the United Kingdom, Dickey and Kearney (2006) reviewed a database of 371 celiac patients diagnosed over a 10 year period. Celiac patients had consumed a gluten-free diet, which was not defined, for 2 years; compliance was assessed through serological testing. 5% of patients were underweight (BMI < 18.5), 57% were normal, 39% were overweight (BMI > 25), including 13% in the obese range (BMI > 30). Of 188 patients compliant with a gluten-free diet, 81% had gained weight after 2 years, including 82% of initially overweight patients.

In a neutral-quality cohort study in Scotland, Dahele and Ghosh (2001) investigated the prevalence of vitamin B-12 deficiency in 39 patients with celiac disease. Median duration of the gluten-free diet, which was not defined, was 4 months (range 2 - 13 months), and compliance was measured through antibody testing. A total of 16 (41%) patients were vitamin B-12 deficient and anemic.

In a neutral-quality cohort study in Sweden, Hallert et al (2002) assessed the vitamin nutrition status of a series of 30 adults with celiac disease living on a gluten-free diet for 10 years. Compliance with the gluten-free diet was assessed by histological evidence of remission and anti-endomysium antibodies. Following the start of treatment, male celiac patients increased in body weight from 70.4 +/- 5.1 kg to 79.2 +/- 10.8 kg (P < 0.001) and females from 62.1 +/- 8.1 kg to 71.0 +/- 10.6 kg (P < 0.001).

In a positive-quality case-control study of 23 celiac children and 23 age- and sex-matched controls in Italy by Rea et al (1996), serum hemoglobin and iron values were below the normal range in more than 50% of patients at diagnosis and within normal ranges in almost all of them after 1 year of gluten-free diet, with which compliance had been monitored by assessment of antigliadin antibody levels. In addition, subjects with iron deficiency received iron supplementation (dose undefined). Serum hemoglobin levels increased from 11.1 +/- 0.4 g/dl to 12.6 +/- 0.2 g/dl (p = 0.001), with 1 patient below the normal range after 1 year of gluten-free diet. Serum iron levels increased from 43 +/- 7 µg/dl to 67 +/- 5 µg/dl (p = 0.01), with 3 patients below the normal range after 1 year of gluten-free diet. Serum hemoglobin, iron, zinc, triglycerides, proteins, albumin and calcium values rose significantly during the year of gluten-free diet.

In a neutral-quality longitudinal study in Argentina by Smecuol et al (1997), of 47 patients with newly diagnosed celiac disease, 25 were reevaluated after a mean duration of gluten-free diet for 37 months (range 25 - 49 months). The gluten-free diet was not defined, but patients were divided into groups based on strict and partial compliance. After treatment, there was a significant increase in body weight (p < 0.0001), fat mass (p < 0.0005), bone mass (p < 0.002) and BMI (p < 0.005) in both groups.

In a positive-quality cross-sectional study by De Lorenzo et al (1999), 43 Italian adolescents with celiac disease were divided into 2 groups based on dietary compliance with a gluten-free diet for more than 1 year ascertained through dietary assessment of food records, clinical evaluation and antibody measurements. 28 were considered fully compliant and 15 were considered partially compliant. All patients had a significantly lower body weight, height, fat-free mass, bone mineral density (p < 0.001) and BMI (p < 0.01) compared with controls. No significant difference was found between patients strictly adherent to a gluten-free diet and patients partially compliant.

In a positive-quality cross-sectional study by Bardella et al (2000) of 71 adults in Italy consuming a strict gluten-free diet without supplementation for over 2 years, with which compliance was measured through food questionnaires and dietitian interview, the weight, height and BMI of male celiac disease patients and the weight and BMI of female celiac disease patients were significantly lower than in control subjects (all P < 0.05).

In a neutral-quality cross-sectional study in the United States, Thompson et al (2005) assessed nutrient intakes and food consumption patterns of adults with celiac disease adhering to a strict gluten-free diet. Mean duration of the gluten-free diet, which was not defined, was 5.3 +/- 4.9 years. 57 participants met inclusion criteria and 47 returned usable food records. Mean BMI was 23.3 +/- 3.1 kg/m2 and ranged from 15.8 - 30.0 kg/m2.

Nutritional Adequacy of the Gluten-Free Dietary Pattern

In a neutral-quality case-control study in Italy, Mariani et al (1998) compared the alimentary habits and diet composition of 47 adolescents with celiac disease and 47 healthy age-matched controls. Analysis of food records and results of antibody levels showed that 25 subjects strictly followed dietetic prescriptions while 22 consumed foods containing gluten, but there were no differences in sex, age, height or weight between these groups. Adolescents with celiac disease and healthy controls consumed normocaloric diets. Lipid and protein consumption was high, and consumption of carbohydrates, calcium, fiber and, especially in girls, iron was low.

In a neutral-quality cohort study in Sweden, Grehn et al (2001) evaluated the dietary habits of 49 celiac patients with longstanding celiac disease and 498 controls. Duration of the gluten-free diet, which was not defined, ranged from 8 - 12 years; compliance was assessed through repeat biopsy and normal serological tests. Celiac patients showed the same energy intake and relative contributions of protein, fat and carbohydrate as controls, but had a lower intake of fiber, niacin, folate, vitamin B-12, calcium, phosphorus and zinc (all P < 0.05).

In the aforementioned neutral-quality cohort study in Sweden, Hallert et al (2002) assessed the vitamin nutrition status of a series of 30 adults with celiac disease living on a gluten-free diet for 10 years. The mean daily intakes of folate and vitamin B-12 were significantly lower in patients than controls (P < 0.05).

In a positive-quality case-control study in Italy, Capristo et al (1997) investigated body composition, energy expenditure, substrate oxidation rate and dietary habits in 16 newly diagnosed patients, 18 patients on a gluten-free diet, and 20 healthy volunteers. Mean duration of the gluten-free diet, which was not defined, was 43.9 months (range 12 - 76 months). Both untreated newly diagnosed celiac patients and patients on a gluten-free diet showed a lower body weight than controls, but energy intake did not differ between groups. Treated patients ate significantly more fat than untreated patients and controls, and the protein intake was lower in celiac disease patients than controls.

In the aforementioned neutral-quality longitudinal study in Argentina by Smecuol et al (1997), of 47 patients with newly diagnosed celiac disease, 25 were reevaluated after a mean duration of gluten-free diet for 37 months (range 25 - 49 months). Mean caloric intake was significantly lower among those with strict adherence than partial adherence (1997 +/- 88 kcal vs 2415 +/- 88 kcals, respectively, p < 0.05).

In the aforementioned positive-quality cross-sectional study by Bardella et al (2000), 71 adults in Italy consumed a strict gluten-free diet without supplementation for over 2 years. Total energy intake was lower in patients than in control subjects (9686 +/- 1569 vs 11297 +/- 1318 kJ per day in males, and 6736 +/- 1318 vs 7740 +/- 1715 kJ per day in females) and the diet contained a higher percentage of energy as fat (P < 0.05) and a lower percentage of energy as carbohydrate (P < 0.01).

In a neutral-quality cross-sectional study by Hopman et al (2006), 219 of 395 members of the Dutch Celiac Society responded to a questionnaire and completed a food record. 132 of the 219 respondents met inclusion criteria and provided informed consent. Mean duration of the gluten-free diet, which was not defined, was 9.6 +/- 6.0 years and strict dietary compliance was reported by 75%. Fiber and iron intakes were significantly lower and the saturated fat intake was significantly higher than recommended but comparable with the general population (all P < 0.05).

In the aforementioned neutral-quality cross-sectional study in the United States, Thompson et al (2005) assessed nutrient intakes and food consumption patterns of adults with celiac disease adhering to a strict gluten-free diet. 57 participants met inclusion criteria and 47 returned usable food records. Mean duration of the gluten-free diet, which was not defined, was 5.3 +/- 4.9 years. Men consumed 88% and women consumed 46% of the recommended amounts of fiber; men consumed 100% and women consumed 44% of the recommended amounts of iron, and men consumed 63% and women consumed 31% of the recommended amounts of calcium.

Summary of research regarding the nutritional adequacy of a gluten-free dietary pattern

listed in order of class and rating

View table in new window

Author/Year

Rating

Study Type

Location

Intervention

Population

Outcomes

Limitations

Kemppainen et al, 1998 A, ø Randomized Controlled Trial Finland Gluten-free diet for 1 year, with or without oats 34 newly diagnosed patients Anthropometric measurements and nutritional laboratory values did not differ among the 3 atrophy groups with the exception of serum ferritin (P < 0.05) and erythrocyte folate (P < 0.05), which were lower in patients with total villous atrophy than in the other groups. Most of the abnormal biochemical values were normalized during 1 year of GFD. 6 subjects dropped out, all from the oat-containing diet group.
Dickey and Kearney, 2006 B; ø Cohort United Kingdom Gluten-free diet for 2 years 371 celiac patients diagnosed over a 10 year period 5% of patients were underweight (BMI < 18.5), 57% were normal, 39% were overweight (BMI > 25), including 13% in the obese range (BMI > 30). Of 188 patients compliant with a gluten-free diet, 81% had gained weight after 2 years, including 82% of initially overweight patients. Authors did not address intentional or unintentional weight loss. Measurement of outcome variables not well described.
Grehn et al, 2001 B; ø Cohort Sweden Gluten-free diet for 8 - 12 years 49 celiac patients with longstanding celiac disease and 498 controls Celiac patients showed the same energy intake and relative contributions of protein, fat and carbohydrate as controls, but had a lower intake of fiber, niacin, folate, vitamin B-12, calcium, phosphorus and zinc (all P < 0.05). Authors note limitations of lack of assessment of fat quality and incomplete data on vitamin and mineral supplements taken by patients.
Dahele and Ghosh, 2001 B; ø Cohort Scotland Gluten-free diet, for a median of 4 months (range 2 - 13 months) 39 patients with celiac disease A total of 16 (41%) patients were vitamin B-12 deficient and anemic. Inclusion/exclusion criteria not well defined. Statistical analysis not described.
Hallert et al, 2002 B; ø Cohort Sweden Gluten-free diet for 10 years 30 adults with celiac disease Following the start of treatment, male celiac patients increased in body weight from 70.4 +/- 5.1 kg to 79.2 +/- 10.8 kg (P < 0.001) and females from 62.1 +/- 8.1 kg to 71.0 +/- 10.6 kg (P < 0.001). The mean daily intakes of folate and vitamin B-12 were significantly lower in patients than controls (P < 0.05). Small sample size. Authors note possible underreporting of dietary intake.
Capristo et al, 1997 C; + Case-Control Study Italy Gluten-free diet for 43.9 months (range 12 - 76 months). 16 newly diagnosed patients, 18 patients on a gluten-free diet, and 20 healthy volunteers. Both untreated newly diagnosed celiac patients and patients on a GFD showed a lower body weight than controls, but energy intake did not differ between groups. Treated patients ate significantly more fat than untreated patients and controls, and the protein intake was lower in celiac disease patients than controls. None.
Rea et al, 1996 C; + Case-Control Study Italy Gluten-free diet for 1 year, subjects with iron deficiency received iron supplementation 23 celiac children and 23 age- and sex-matched controls Serum hemoglobin levels increased from 11.1 +/- 0.4 g/dl to 12.6 +/- 0.2 g/dl (p = 0.001), with 1 patient below the normal range after 1 year of gluten-free diet. Serum hemoglobin, iron, zinc, triglycerides, proteins, albumin and calcium values rose significantly during the year of gluten-free diet. Authors note small sample size and lack of homogeneity in subject age.
Mariani et al, 1998 C, ø Case-Control Study Italy Gluten-free diet; 25 subjects strictly followed dietetic prescriptions while 22 consumed foods containing gluten 47 adolescents with celiac disease and 47 healthy age-matched controls Adolescents with celiac disease and healthy controls consumed normocaloric diets. Lipid and protein consumption was high, and consumption of carbohydrates, calcium, fiber and especially in girls, iron was low. Inclusion/exclusion criteria not well described. Controls were not sex-matched.
Smecuol et al, 1997 C, ø Longitudinal Study Argentina Gluten-free diet for a mean duration of 37 months (range 25 - 49 months). 25 patients with newly diagnosed celiac disease. After treatment, there was a significant increase in body weight (p < 0.0001), fat mass (p < 0.0005), bone mass (p < 0.002) and BMI (p < 0.005) in both groups. However, mean caloric intake was significantly lower among those with strict adherence than partial adherence (1997 +/- 88 kcal vs 2415 +/- 88 kcals, respectively, p < 0.05). Only 25 of 47 patients seen after several years. No power calculations done.
Bardella et al, 2000 D, + Cross-Sectional Study Italy Strict GFD without supplementation for over 2 years 71 adults with celiac disease The weight, height and BMI of male patients and the weight and BMI of female patients were significantly lower than in control subjects (all P < 0.05). Total energy intake was lower in patients than in control subjects (9686 +/- 1569 vs 11297 +/- 1318 kJ per day in males, and 6736 +/- 1318 vs 7740 +/- 1715 kJ per day in females) and the diet contained a higher percentage of energy as fat (P < 0.05) and a lower percentage of energy as carbohydrate (P < 0.01). Author notes that observed differences in anthropometric measurements and body composition seem to be justified by lower daily energy intakes of celiac disease patients.
De Lorenzo et al, 1999 D, + Cross-Sectional Study Italy 28 were considered fully compliant and 15 were considered partially compliant with GFD for more than 1 year. 43 adolescents with celiac disease All patients had a significantly lower body weight, height, fat-free mass, bone mineral density (p < 0.001) and BMI (p < 0.01) compared with controls. No significant difference was found between patients strictly adherent to a gluten-free diet and patients partially compliant. None.
Hopman et al, 2006 D, ø Cross-Sectional Study The Netherlands Gluten-free diet for a mean duration of 9.6 +/- 6.0 years. 132 members of the Dutch Celiac Society Fiber and iron intakes were significantly lower and the saturated fat intake was significantly higher than recommended but comparable with the general population (all P < 0.05). Self-reported height and weight. Significant differences between responders and non-responders
Thompson et al, 2005 D, ø Cross-Sectional Study United States Strict gluten-free diet for a mean of 5.3 +/- 4.9 years 47 adults with celiac disease Men consumed 88% and women consumed 46% of the recommended amounts of fiber; men consumed 100% and women consumed 44% of the recommended amounts of iron, and men consumed 63% and women consumed 31% of the recommended amounts of calcium. Small sample size and possible bias of survey participants may not be representative of larger celiac community. Statistical analysis not described.




Quality Rating Summary
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Worksheets
Bardella MT, Fredella C, Prampolini L, Molteni N, Giunta AM, Bianchi PA. Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet. Am J Clin Nutr. 2000; 72: 937-939.

Capristo E, Mingrone G, Addolorato G, Greco AV, Corazza GR, Gasbarrini G.  Differences in metabolic variables between adult celiac patients at diagnosis and patients on a gluten-free diet.  Scand J Gastronenterol 1997;32(12):1222-9.

Dahele A, Ghosh S.  Vitamin B12 deficiency in untreated celiac disease.  Am J Gastroenterol 2001;96(3):745-750.

De Lorenzo A, Di Campli C, Andreoli A, Sasso GF, Bonamico M, Gasbarrini A.  Assessment of body composition by bioelectrical impedance in adolescent patients with celiac disease.  Am J Gastroenterol 1999 Oct; 94(10): 2951-2955. 

Dickey W, Kearney N.  Overweight in celiac disease:  prevalence, clinical characteristics, and effect of a gluten-free diet.  Am J Gastroenterology 2006;101:2356-2359.

Grehn S, Fridell K, Lilliecreutz M, Hallert C.  Dietary habits of Swedish adult celiac patients treated by a gluten-free diet for 10 years.  Scand J Nutrition 2001;45:178-182.

Hallert C, Grant C, Grehn S, Granno C, Hulten S, Midhagen G, Strom M, Svensson H, Valdimarsson T.  Evidence of poor vitamin status in celiac patients on a gluten-free diet for 10 years.  Aliment Pharmacol Ther 2002;16:1333-1339.

Hopman EGD, le Cessie S, von Blomberg BME, Mearin ML.  Nutritional management of the gluten-free diet in young people with celiac disease in the Netherlands.  J Pediatr Gastroenterol Nutr 2006;43:102-108.

Kemppainen TA, Kosma VM, Janatuinen EK, Julkunen RJ, Pikkarainen PH, Uusitupa MI.  Nutritional status of newly diagnosed celiac disease patients before and after the institution of a celiac disease diet - association with the grade of mucosal villous atrophy.  Am J Clin Nutr 1998; 67(3): 482-487.

Mariani P, Viti MG, Montuori M, La Vecchia A, Cipolletta E, Calvani L, Bonamico M.  The gluten-free diet:  a nutritional risk factor for adolescents with celiac disease?  J Pediatr Gastroenterol Nutr 1998;27:519-523.   

Rea F, Polito C, Marotta A, Di Toro A, Iovene A, Collini R, Rea L, Sessa G.  Restoration of body composition in celiac children after one year of gluten-free diet.  J of Pediatric Gastroenterology and Nutrition 1996; 23: 408-412.

Smecuol E, Gonzalez D, Mautalen C, Siccardi A, Cataldi M, Niveloni S, Mazure R, Vazquez H, Pedreira S, Soifer G, Boerr LA, Maurino E, Bai JC.  Longitudinal study on the effect of treatment on body composition and anthropometry of celiac disease patients.  Am J Gastroenterol 1997;92(4):639-43.

Thompson T, Dennis M, Higgins LA, Lee AR, Sharrett MK.  Gluten-free diet survey:  are Americans with celiac disease consuming recommended amounts of fibre, iron, calcium, and grain foods?  J Hum Nutr Diet 2005;18(3):163-9.

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