SUMMARYBackground: Patients with coeliac disease are advised to keep to a lifelong gluten-free diet to remain well. Uncertainty still exists as to whether this gives a nutritionally balanced diet. Aim: To assess the vitamin nutrition status of a series of coeliac patients living on a gluten-free diet for 10 years. Methods: Thirty adults with coeliac disease (mean age, 55 years; range, 45-64 years; 60% women), in biopsyproven remission following 8-12 years of dietary treatment, were studied. We measured the total plasma homocysteine level, a metabolic marker of folate, vitamin B-6 and vitamin B-12 deficiency, and related plasma vitamin levels. The daily vitamin intake level was assessed using a 4-day food record. Normative data were obtained from the general population of the same age.Results: Coeliac patients showed a higher total plasma homocysteine level than the general population, indicative of a poor vitamin status. In accordance, the plasma levels of folate and pyridoxal 5¢-phosphate (active form of vitamin B-6) were low in 37% and 20%, respectively, and accounted for 33% of the variation of the total plasma homocysteine level (P < 0.008). The mean daily intakes of folate and vitamin B-12, but not of vitamin B-6, were significantly lower in coeliac patients than in controls. Conclusions: Half of the adult coeliac patients carefully treated with a gluten-free diet for several years showed signs of a poor vitamin status. This may have clinical implications considering the linkage between vitamin deficiency, elevated total plasma homocysteine levels and cardiovascular disease. The results may suggest that, when following up adults with coeliac disease, the vitamin status should be reviewed.
Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations .11 450 pmol/8610 8 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
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