B vitamins related to homocysteine metabolism in adults celiac disease patients: a cross-sectional study
© Valente et al. 2015
Received: 9 March 2015
Accepted: 9 October 2015
Published: 20 October 2015
The only treatment for celiac disease is the gluten-free diet. Few studies have assessed the nutritional adequacy of this diet, especially of B vitamins related to homocysteine metabolism. The aim of this study was to assess the nutritional status and serum concentrations of B vitamins involved in homocysteine metabolism, and to determine whether the dietary intake of these vitamins are meeting Dietary Reference Intakes in celiac patients.
A cross-sectional study enrolled a total of 20 celiac patients (36.3 ± 13.7 years old; 65 % women), following strict gluten-free diet (GFD) and 39 healthy controls matched by sex and age. The dietary intake was assessed by 3-day food records, and serum concentrations of homocysteine and vitamins B6, B12, and folate were determined after overnight fasting. Comparisons between the two groups were performed by Student’s t test or Mann–Whitney U-test, for continuous variables. Pearson’s chi-square test or Fisher’s exact test was used for categorical variables. An alpha level of 5 % were considered significant.
Celiac patients had lower serum folate concentrations (7.7 ± 3.5 ng/mL, P < 0.05) than controls. All celiac patients had folate intake below the Estimated Average Requirement (EAR) (130.8 ± 53.6 μg/d). However, only a small proportion of celiac patients had hyperhomocysteinemia.
Celiac patients treated with GFD presented inadequacy of dietary folate intake and low-serum concentrations of folate, suggesting that more attention should be given to the quality of the nutrients offered by the GFD, as it constitutes a lifelong treatment.
KeywordsCeliac disease Gluten-free diet Folate Homocysteine
Celiac disease (CD) is a systemic autoimmune disorder developed in genetically predisposed individuals by the ingestion of gluten . CD is characterized by an inflammatory process that occurs in the small intestine resulting in flattening of the villi and loss of absorptive function . The only treatment for CD is the total exclusion of gluten from the diet avoiding its food source, such as wheat, rye, and barley .
Folate and vitamins B6 and B12 are, respectively, substrate and essential cofactors for enzymes in homocysteine metabolism, which is an intermediate metabolite of methionine synthesis pathway . Inadequate intake of those vitamins is the most common cause of high concentrations of serum homocysteine . About two thirds of hyperhomocysteinemia cases are related to low or moderate serum concentration of these vitamins, especially folate .
In turn, hyperhomocysteinemia in untreated celiac patients has been linked to common characteristics of this disease such as abortions , osteoporosis , and cardiovascular disease . Although some authors have shown hyperhomocysteinemia in treated celiac patients [13, 14], few studies have evaluated the role of GFD in providing adequate amounts of nutrients. Thus, the aim of this study was to assess the nutritional status and serum concentrations of B vitamins involved in homocysteine metabolism, and to determine whether the dietary intake of these vitamins is meeting Dietary Reference Intakes (DRI) in treated celiac patients.
In both groups, subjects were excluded if they tested positive for the IgA anti-transglutaminase antibody (≥7.0 U/mL), presented recurrent gastrointestinal symptoms, used vitamins and minerals supplements, as well as pregnant and lactating women. Both groups were studied at the same period, and all measurements were performed at the same clinical chemistry laboratory by the same researcher.
The study was approved by the Ethics Committee on Human Research of the Universidade Federal de Viçosa (Protocol number 146/2011). Written informed consent was obtained from all of the subjects.
Weight and height were measured to calculate the body mass index (BMI) . Subjects with BMI below 24.9 kg/m2 were considered eutrophics. The waist circumference was measured at the midpoint between the bottom margin of the last palpable rib and the iliac crest . Total body fat was measured by dual-energy X-ray radiological absorptiometry (DXA, GE Lunar Prodigy, General Electric Medical Systems, Milwaukee, WI, USA). The Fat Mass Index (FMI), calculated by the ration between the weight of fat (kg) and the square of height (m2), was used as indicative of body fat adequacy. Results above 6 kg/m2 for men and 9 kg/m2 for women were considered excess of body fat .
Dietary intake was assessed using a three non-consecutive day food records. All volunteers were trained prior to filling out the questionnaire. Subjects were also instructed not to change their usual eating pattern. All records were reviewed by an trained nutritionist. The average daily nutrient intake was calculated using Avanutri Revolution® software version 4.0 (Avanutri & Nutrição Serviços e Informática Ltda., Brazil), using food composition data from TACO  and IBGE  tables.
For the assessment of folate and vitamin B6 intake adequacy, there were considered adequate intake values above the Estimated Average Requirement (EAR) (folate = 320 μg/day; B6 = 1.4 mg/day) and below the Tolerable Upper Intake (UL) (folate = 1000 μg/day; vitamin B6 = 100 mg/day) . As vitamin B12 has no UL established, intake above the EAR (2.0 μg/day) was considered appropriate.
After overnight fast, 20 mL of blood was collected from all the volunteers. The IgA anti-transglutaminase antibody was analyzed by Enzyme- Linked Immuno Sorbent Assay (ELISA) (Celikey® IgA, Phadia AB, Uppsala, Sweden), and homocysteine (Immulite2000, Siemens, USA), vitamin B12, and serum folate (Modular e170, Roche, Switzerland) by chemiluminescence. Vitamin B6 was determined through the analysis of pyridoxal-5-phosphate (PLP), isomer of highest concentration in human plasma, through High-Performance Liquid Chromatography with fluorescence detection [23, 24].
Statistical analyses were performed using Stata software (StataCorp LP, USA, version 9.0). Comparisons between the two groups were performed by Student’s t test or Mann–Whitney U-test test. The tests depended on the distribution of the variables according to Shapiro–Wilk normality test. For the comparison of proportions, Pearson’s chi-square test or Fisher’s exact test was used. Results were expressed as mean ± standard deviation (s.d.). Values of P < 0.05 were considered significant.
The power of the present study was 98 % calculated according to Martínez-González et al.  and based on serum concentration of folate as main variable.
Characteristics of celiac patients and healthy controls
36.3 ± 13.7
36.0 ± 13.0
22.5 ± 3.2
23.8 ± 3.7
10.4 ± 3.1
10.7 ± 3.3
Waist circumference (cm)
76.5 ± 10.3
80.0 ± 11.3
113.6 ± 2.2
112.9 ± 2.0
74.3 ± 1.9
74.0 ± 1.5
4.8 ± 0.1
4.5 ± 0.1
Total Cholesterol (mmol/L)
4.9 ± 0,2
4,6 ± 0.4
HDL cholesterol (mmol/L)
2.7 ± 0.2
2.6 ± 0.1
LDL cholesterol (mmol/L)
6.7 ± 0.2
6.0 ± 0.1
1.5 ± 0.2
1.2 ± 0.1
Biochemistry parameters of celiac patients and healthy controls
13.6 ± 1.2
13.4 ± 1.3
10.0 ± 3.2
9.3 ± 2.5
17.5 ± 8.0*
29.0 ± 9.4
Vitamin B6 (nmol/L)
130.3 ± 35.8
130.3 ± 52.3
Vitamin B12 (pg/mL)
271.1 ± 89.0
257.3 ± 90.6
Daily intake of energy, macronutrients, fiber, and vitamins of celiac patients and healthy controls
8460.3 ± 2,559.8
9535.0 ± 4,225.1
256.8 ± 74.2
273.8 ± 67.3
81.6 ± 28.6
86.6 ± 25.6
74.3 ± 32.1
72.6 ± 23.8
18.4 ± 7.1
17.8 ± 6.5
133. 2 ± 62.5
140.9 ± 65.8
Vitamin B6 (mg/d)
2.4 ± 1.6
2.6 ± 1.3
Vitamin B12 (μg/d)
2.1 ± 1.9
2.4 ± 5.6
Despite the inadequate intake and lower serum concentrations of folate, serum homocysteine in celiac patients ranged from 5.3 to 16.3 μmol/L and in controls from 5.2 to 15.3 μmol/L (Table 2). Only 1 patient in each group presented hyperhomocysteinemia (>15 μmol/L). For males, the celiac patients showed an average homocysteine concentration of 11.4 ± 3.13 μmol/L, while the average in the control group it was of 10.7 ± 3.08 μmol/L (P > 0.05). For celiac and control females, these values were 9.3 ± 3.12 and 8.5 ± 1.6 μmol/L (P > 0.05), respectively.
The results of our study showed that celiac patients presented lower serum concentrations and inadequate folate consumption. However, they did not present hyperhomocysteinemia. Folate deficiency in newly diagnosed and untreated celiac patients is already well described. Dickey et al.  observed that newly diagnosed celiac patients presented lower concentrations of eritrocitary and serum folate than controls and celiac patients under GFD for at least 1 year. Wierdsma et al.  observed 20 % folate deficiency in these patients, while Saibeni et al.  observed 43.5 %. Therefore, celiac patients present risk of developing this deficiency 5.1 times higher than healthy individuals. This is probably related to the loss of proximal small intestine villi resulting in malabsorption of micronutrients in untreated patients. Thus, the higher the degree of vilositary atrophy, the higher the folate deficiency .
Adherence to a strict GFD throughout life is the only known treatment for celiac disease . Some factors, such low age at diagnosis, life stages (childhood and adolescence)  and higher cost of this diet  contribute to treatment non-adherence. Although celiac disease has being a female-predominant disease , gender is not a factor that affects the treatment adherence [30, 31] Thus, our population profile was compatible with a good gluten-free diet adherence.
This treatment aims the regeneration of the intestinal villi with reduced risk of complications related to nutrients malabsorption and improvement of nutritional status . The expected histological recovery of the intestinal mucosa is within 6 to 12 months after the onset of GFD  resulting in improvement of symptoms .
Although some studies have demonstrated improvement on folate status after 6 months  and 1 year  of treatment, our study showed that even after an average of 1.2 ± 0.6 years of treatment, celiac disease patients still have lower serum folate concentrations when compared to controls. In general, the full recovery of the intestinal mucosa after exclusion of gluten from diet occurs in a minority of patients, and most commonly the remission of histological lesion is observed, but with persistence of the lymphocytic infiltrate . This remission occurs slowly and progressively and is influenced by age, the degree of initial injury, and adherence to GFD . Thus, we believe that histological lesions remission could have been slower because of severe injuries on adult patients (Marsh III B and C) at the diagnosis, despite a period of more than twelve months of treatment.
However, Dickey et al.  did not observe any differences in serum folate concentrations when comparing patients in total or partial recovery of intestinal villi and control. Furthermore, Hallert et al.  observed folate deficiency in 37 % of celiac patients under treatment with GFD for 10 years and suggest that other factors, such as inadequate nutrient consumption, may have contributed to this results.
In this study, although we did not observe difference in nutrient intake between celiac patients and controls, 100 and 56.6 % of celiac patients showed inadequate folate and vitamin B12 consumption, respectively. Despite the importance of the GFD on celiac patient’s health, there is a paucity of studies assessing the nutritional adequacy of this diet.
Recent studies that compared the consumption of vitamins in treated celiac patients and healthy controls observed deficiency on vitamins B1, B2, B6, and folate intake [38–40]. However, to the extent of our knowledge, only two studies [41, 42] compared the vitamin intake adequacy in relation to nutritional recommendations, in order to show the real supply of nutrients by GFD.
The hypothesis for these nutritional deficiencies are based on intake of gluten-free products, which are often produced with refined flours with no fortification [37, 43], and the inadequacy of the habits and food choices of celiac patients [44, 45]. Thompson , analyzing the nutritional composition of wheat replacer food concluded that most of these products were not a natural source of or enriched with vitamins B1, B2, B3, folate, and iron. Still, Lee et al.  showed that the celiac population did not reach the minimum recommendation of six servings of whole grains a day, needed to achieve adequate intake of folate.
Associated with these factors, a low demand for nutritional counseling with a health-care professional, such as nutritionist, as found in this study, may favor for cases of inadequate food consumption. GFD is simple in its principles; however, to completely eliminate all foods and ingredients that contain gluten is a task that requires a lot of effort and commitment . Health professionals have the role of guiding the patients so that GFD could be healthy, interesting, and practical . These goals are difficult to be achieved for patients who are not professionally oriented because the diet imposed is restrictive, and the changes required are difficult and permanent .
The hyperhomocysteinemia occurrence may be related to both vitamin deficiency and genetic abnormalities of methyltetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) enzymes . Despite of heterozygous and homozygous prevalence of mutations on MTFHR be 42-47 % and 9-17 %,  and on MTRR be 50 % and 19-29 %, respectively in the general population,  in celiac patients this prevalence is approximately 21 % for both enzymes , suggesting that there is no important role of these mutations in developing hyperhomocysteinemia in these patients .
Deficiency of folate in the long term may result in the elevation of the serum concentrations of homocysteine with greater risk of developing coronary conditions [53, 54]. Although in our study we observed serum and intake deficiencies of folate in celiac patients, only 1 (6.6 %) patient presented hyperhomocysteinemia. In untreated patients, the prevalence of hyperhomocysteinemia ranged from 20 [28, 54] to 46 % . In treated patients, studies evaluating this prevalence are still scarce. Zanini et al.  observed 24 % prevalence of hyperhomocysteinemia in patients under treatment for 1 to 5 years, while Hallert et al.  found hyperhomocysteinemia in patients undergoing GFD for 10 years.
Moreover, Dickey et al.  and Saibeni et al.  observed serum homocysteine reduction after 1 year of GFD, while De Marchi et al.  did not observe this effect after 6–8 months of treatment. Thus, more studies are needed to establish the relationship between the adhesion to GFD and serum homocysteine concentrations.
Our findings demonstrated inadequacy of dietary intake and low-serum levels of folate in celiac patients treated with GFD. It is suggested that more attention should be given to the quality of the nutrients offered by GFD because this constitutes a treatment for life.
Body mass index
Fat mass index
Dietary reference intake
Estimated average requirement
This work was supported by the Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Belo Horizonte, Brazil. The Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Brasília, Brazil provided research grants to FXV, TNC and LFSM. HHMH and MCGP are Coordenação Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) fellows.
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- Branski D. New insights in celiac disease. Rambam Maimonides Med J. 2012;3(1):e0006.View ArticlePubMedPubMed CentralGoogle Scholar
- Di Sabatino A, Corazza GR. Coeliac disease. Lancet. 2009;373:1480–93.View ArticlePubMedGoogle Scholar
- Thompson T. Celiac Disease: what gluten-free means today. Practical Gastroenterol. 2012;19–26.
- Hopman EG, Le Cessie S, Von Blomberg BM, Mearin ML. Nutritional management of the gluten-free diet in young people with celiac disease in The Netherlands. J Pediatr Gastroenterol Nutr. 2006;43:102–8.View ArticlePubMedGoogle Scholar
- Hallert C, Svensson M, Tholstrup J, Hultberg B. B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther. 2009;29:811–6.View ArticlePubMedGoogle Scholar
- Hadithi M, Mulder CJ, Stam F, Azizi J, Crusius JB, Peña AS, et al. Effect of B vitamin supplementation on plasma homocysteine levels in celiac disease. World J Gastroenterol. 2009;15:955–60.View ArticlePubMedPubMed CentralGoogle Scholar
- McCully KS. Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr. 2007;86:1563S–8S.PubMedGoogle Scholar
- Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc. 2008;83:1203–12.View ArticlePubMedGoogle Scholar
- Voutilainen S, Virtanen JK, Rissanen TH, Alfthan G, Laukkanen J, Nyyssönen K, et al. Serum folate and homocysteine and the incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr. 2004;80:317–23.PubMedGoogle Scholar
- Bergen NE, Jaddoe VW, Timmermans S, Hofman A, Lindemans J, Russcher H, et al. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG. 2012;119:739–51.View ArticlePubMedGoogle Scholar
- Tyagi N, Vacek TP, Fleming JT, Vacek JC, Tyagi SC. Hyperhomocysteinemia decreases bone blood flow. Vasc Health Risk Manag. 2011;7:31–5.PubMedPubMed CentralGoogle Scholar
- De Marchi S, Chiarioni G, Prior M, Arosio E. Young adults with coeliac disease may be at increased risk of early atherosclerosis. Aliment Pharmacol Ther. 2013;38:162–9.View ArticlePubMedGoogle Scholar
- Lim PO, Tzemos N, Farquharson CA, Anderson JE, Deegan P, MacWalter RS, et al. Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction. J Hum Hypertens. 2002;16:411–5.View ArticlePubMedGoogle Scholar
- Gefel D, Doncheva M, Ben-Valid E, el Wahab-Daraushe A, Lugassy G, Sela BA. Recurrent stroke in a young patient with celiac disease and hyperhomocysteinemia. Isr Med Assoc J. 2002;4:222–3.PubMedGoogle Scholar
- Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterol. 1992;102:330–54.View ArticleGoogle Scholar
- Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol. 1999;11:1185–94.View ArticlePubMedGoogle Scholar
- World Health Organization. Phisycal Status: the use and Interpretation of Anthropometry. In: Committee RoaWe, editor. WHO Technical Report Series 894. Geneva: World Health Organization; 1995.Google Scholar
- World Health Organization. Waist circunference and waist-hip ratio. In: Consultation RoaWe. Geneva: World Health Organization; 2008.Google Scholar
- Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, et al. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013;7:304–83.View ArticlePubMedGoogle Scholar
- FCF-USP. Tabela Brasileira de Composição de Alimentos. TBCA. Faculdade de Ciências Farmacêuticas da USP. 2010.
- IBGE – Instituto Brasileiro de Geografia e Estatística. Pesquisa de Orçamentos Familiares 2008–2009. Rio de Janeiro: Tabela de Composição Nutricional dos Alimentos Consumidos no Brasil; 2011.Google Scholar
- Institute of Medicine. Dietary References Intakes. Washington, DC: The National Academy Press; 2002.Google Scholar
- Kimura M, Kanehira K, Yokoi K. Highly sensitive and simple liquid chromatographic determination in plasma of B6 vitamers, especially pyridoxal 5'-phosphate. J Chromatogr A. 1996;722:295–301.View ArticlePubMedGoogle Scholar
- Deitrick CL, Katholi RE, Huddleston DJ, Hardiek K, Burrus L. Clinical adaptation of a high-performance liquid chromatographic method for the assay of pyridoxal 5'-phosphate in human plasma. J Chromatogr B Biomed Sci Appl. 2001;751:383–7.View ArticlePubMedGoogle Scholar
- Martínez-González MA, Alonso A, Rastrollo MB. Estimación del tamaño muestral. In: Martínez-González MA, Sánchez-Villegas A, Fojardo JF, editors. Bioestadística Amigable. España: Diaz de Santos; 2009. p. 373–96.Google Scholar
- Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, et al. Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery. Scand J Gastroenterol. 2008;43:682–8.View ArticlePubMedGoogle Scholar
- Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013;5:3975–92.View ArticlePubMedPubMed CentralGoogle Scholar
- Saibeni S, Lecchi A, Meucci G, Cattaneo M, Tagliabue L, Rondonotti E, et al. Prevalence of hyperhomocysteinemia in adult gluten-sensitive enteropathy at diagnosis: role of B12, folate, and genetics. Clin Gastroenterol Hepatol. 2005;3:574–80.View ArticlePubMedGoogle Scholar
- 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;67:482–7.PubMedGoogle Scholar
- Kurppa K, Lauronen O, Collin P, Ukkola A, Laurila K, Huhtala H, et al. Factors associated with dietary adherence in celiac disease: a nationwide study. Digestion. 2012;86:309–14.View ArticlePubMedGoogle Scholar
- Villafuerte-Galvez J, Vanga RR, Dennis M, Hansen J, Leffler DA, Kelly CP, et al. Factors governing long-term adherence to a gluten-free diet in adult patients with coeliac disease Aliment. Pharmacol Ther. 2015;42:753–60.Google Scholar
- Bai D, Brar P, Holleran S, Green PHR RR. Effect of gender on the manifestations of celiac disease: Evidence for greater malabsorption in men. Scand J Gastroenterol. 2005;40:183–7.View ArticlePubMedGoogle Scholar
- Garcia-Manzanares A, Lucendo AJ. Nutritional and dietary aspects of celiac disease. Nutr Clin Pract. 2011;26:163–73.View ArticlePubMedGoogle Scholar
- Wahab PJ, Meijer JW, Mulder CJ. Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery. Am J Clin Pathol. 2002;118:459–63.View ArticlePubMedGoogle Scholar
- Zanini B, Mazzoncini E, Lanzarotto F, Ricci C, Cesana BM, Villanacci V, et al. Impact of gluten-free diet on cardiovascular risk factors. A retrospective analysis in a large cohort of coeliac patients. Dig Liver Dis. 2013;45:810–5.View ArticlePubMedGoogle Scholar
- Lanzini A, Lanzarotto F, Villanacci V, Mora A, Bertolazzi S, Turini D, et al. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Aliment Pharmacol Ther. 2009;29:1299–308.View ArticlePubMedGoogle Scholar
- Hallert C, Grant C, Grehn S, Grännö C, Hultén S, Midhagen G, et al. Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years. Aliment Pharmacol Ther. 2002;16:1333–9.View ArticlePubMedGoogle Scholar
- Wild D, Robins GG, Burley VJ, Howdle PD. Evidence of high sugar intake, and low fibre and mineral intake, in the gluten-free diet. Aliment Pharmacol Ther. 2010;32:573–81.View ArticlePubMedGoogle Scholar
- Shepherd SJ, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013;26:349–58.View ArticlePubMedGoogle Scholar
- Martin J, Geisel T, Maresch C, Krieger K, Stein J. Inadequate nutrient intake in patients with celiac disease: results from a german dietary survey. Digestion. 2013;87:240–6.View ArticlePubMedGoogle Scholar
- Thompson T, Dennis M, Higgins LA, Lee AR, Sharrett MK. Gluten-free diet survey: are Americans with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods? J Hum Nutr Diet. 2005;18:163–9.View ArticlePubMedGoogle Scholar
- Kinsey L, Burden ST, Bannerman E. A dietary survey to determine if patients with coeliac disease are meeting current healthy eating guidelines and how their diet compares to that of the British general population. Eur J Clin Nutr. 2008;62:1333–42.View ArticlePubMedGoogle Scholar
- Pagano AE. Whole grains and the gluten-free diet. Practical Gastroenterology 2006;29:66–78.
- Kupper C. Dietary guidelines and implementation for celiac disease. Gastroenterol. 2005;128:S121–7.View ArticleGoogle Scholar
- Raymond N. The gluten-free diet: an update for health professionals. Practical Gastroenterology 2006;9:73–91.
- Thompson T. Thiamin, riboflavin, and niacin contents of the gluten-free diet: is there cause for concern? J Am Diet Assoc. 1999;99:858–62.View ArticlePubMedGoogle Scholar
- Lee AR, Ng DL, Dave E, Ciaccio EJ, Green PH. The effect of substituting alternative grains in the diet on the nutritional profile of the gluten-free diet. J Hum Nutr Diet. 2009;22:359–63.View ArticlePubMedGoogle Scholar
- See J, Murray JA. Gluten-free diet: the medical and nutrition management of celiac disease. Nutr Clin Pract. 2006;21:1–15.View ArticlePubMedGoogle Scholar
- Santilli F, Davì G, Patrono C. Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective. Vascular pharmacology. 2015;15:S1537–1891.Google Scholar
- Deloughery TG, Evans A, Sadeghi A, McWilliams J, Henner WD, Junior TLM, et al. Common mutation in methylenetetrahydrofolate reductase: correlation with homocysteine metabolism and late-onset vascular disease. Circulation. 1996;94:3074–8.View ArticlePubMedGoogle Scholar
- Jacques PF, Bostom AG, Selhub J, Rich S, Ellison RC, Eckfeldt JH, et al. Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI. Family Heart Study. 2003;166:49–55.Google Scholar
- Casella G, Bassotti G, Villanacci V, Di Bella C, Pagni F, Corti GL, et al. Is hyperhomocysteinemia relevant in patients with celiac disease? World J Gastroenterol. 2011;17:2941–4.View ArticlePubMedPubMed CentralGoogle Scholar
- Voutilainen S, Lakka TA, Porkkala-Sarataho E, Rissanen T, Kaplan GA, Salonen JT. Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr. 2000;54:424–8.View ArticlePubMedGoogle Scholar
- De Bree A, Verschuren WM, Blom HJ, Nadeau M, Trijbels FJ, Kromhout D. Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study. Atherosclerosis. 2003;166:369–77.View ArticlePubMedGoogle Scholar