B Vitamin Supplementation Lowers Risk for Hyperhomocysteinemia in Patients With Celiac Disease

March 12, 2009

March 12, 2009 — Dietary supplementation with B vitamins reduces homocysteine levels in patients with celiac disease, according to a study published in the February 28 issue of the World Journal of Gastroenterology.

"Celiac disease is a typical example of a malabsorption syndrome conferring increased risk for various deficiency states, including folate and vitamin B12," explain Muhammed Hadithi, MD, from the Department of Gastroenterology, VU University Medical Center in Amsterdam, the Netherlands, and colleagues. "Moreover, hyperhomocysteinemia is significantly more frequent in patients with newly diagnosed celiac disease than healthy controls and has been reported to improve after the institution of a gluten-free diet."

Previous studies have indicated that hyperhomocysteinemia is associated with atherothrombotic vascular disease. Thus, the current study was designed to evaluate the effect of daily supplementation with vitamin B6, folate, and vitamin B12 on total plasma homocysteine (tHcy) levels in patients with celiac disease.

A total of 51 consecutive adults with celiac disease and 50 healthy control individuals matched for age and sex were evaluated for levels of serum vitamin B6, folate, vitamin B12, and fasting tHcy. Approximately half of the patients with celiac disease (49%) reported regular daily use of vitamin supplements containing vitamin B6, folate, and vitamin B12, whereas none of the control patients reported the use of vitamin supplementation. In addition, C677T polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) was assessed in all of the control patients and in 46 of the patients with celiac disease.

The results of the study indicated that patients with celiac disease who took daily vitamin supplements had lower tHcy levels compared with patients who did not take vitamins (P = .001) and healthy control patients (P = .003). Furthermore, tHcy was slightly, yet significantly, higher in patients with celiac disease who did not use vitamins vs control patients (P = .04). Multiple regression analyses revealed that vitamin B6 and folate intake was significantly and independently associated with tHcy, whereas vitamin B12 intake was not. There was no significant difference in the prevalence of the MTHFR thermolabile variant T-allele between patients with celiac disease and the control patients (P = .89).

In the study, patients with celiac disease were further categorized into 4 groups to evaluate whether villous atrophy affects the protective role of B vitamin supplements against hyperhomocysteinemia. The groups included those newly diagnosed, those with persistent villous atrophy at follow-up as a result of dietary mistakes, those with persistent villous atrophy at follow-up despite strict adherence to a gluten-free diet for a year, and those with recovered villous architecture at follow-up biopsy. An evaluation of patients after stratification according to small bowel histology demonstrated that villous atrophy was associated with higher tHcy levels (P = .018). However, vitamin B6, folate, and vitamin B12 levels remained comparable.

"This study demonstrated that patients with celiac disease using B vitamin supplements had lower tHcy levels than those who did not use B vitamin supplements. Second, even if villous atrophy persists, B-vitamin supplements can normalize B6, folate, B12 status, and tHcy levels. Finally, both the presence and the severity of celiac disease were determinants of tHcy levels, independent of measured B-vitamin status," the authors explain.

Potential limitations of this study include the fact that the heterogeneity of study participants influenced the design of the study. Furthermore, there was no standardization of B vitamin supplementation and no follow-up data. Consequently, researchers could not evaluate the effect of a gluten-free diet alone on tHcylevels.

"A useful [future] study would be to randomize newly diagnosed patients with celiac disease to use B-vitamin supplements with a gluten free diet compared to a gluten free diet alone," conclude Dr. Hadithi and colleagues.

World J Gastroenterol. 2009;15:955–960.

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