OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine. Vitamin B12 and folate deficiency and with antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to hyperhomocysteinemia. The known associations between hyperhomocysteinemia and smoking, osteoporosis, and thrombosis make it an interesting candidate as a pathogenetic link in IBD. The aim of this study was to identify the prevalence and risk factors of hyperhomocysteinemia in patients with IBD.
METHODS: Sixty-five consecutive IBD patients were recruited from a tertiary outpatient gastroenterology practice. Fasting plasma homocysteine levels were measured, along with vitamin B12 and folate. Data regarding medication use, multivitamin use, disease location and severity, and extraintestinal manifestations of IBD were gathered. Homocysteine levels in 138 healthy control subjects were compared with the IBD cohort, and adjustments for age and sex were made using logistic regression. Multivariate analysis was performed to seek predictors of homocysteine levels.
RESULTS: The mean age in the IBD cohort was 42 ± 13.4 yr (±SD), and 43% were male. The mean disease duration was 13.8 ± 9.4 yr, and 32% had used steroids within the last 3 months. Immunomodulator had been used in 32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of patients. Five patients had experienced venous thrombosis or stroke, but only one of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine levels in the IBD cohort cases and controls were 8.7 and 6.6 μmol/L, respectively (p< 0.05). IBD significantly increased the risk of hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5–24]). Advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin were independently associated with higher homocysteine levels in the multivariate analysis (R2 = 0.55; p = 0.001).
CONCLUSIONS: Hyperhomocysteinemia is significantly more common in patients with IBD compared with healthy controls, and is associated with lower (but not necessarily deficient) vitamin B12 levels.
Commentary by Dr. Calapai:
Homocysteine is a significant risk factor for cardiovascular disease and plaque accumulation in blood vessels. Research goes back thirty years or so. It elevates when levels of B6, B12, and folic acid are too low. The requirements for these nutrients can vary depending upon age, activity and absorptive/ digestive ability. In any case, we need to assess homocysteine levels along with the vitamins to help to change the course of vascular inflammation.
These vitamins should come in a comprehensive multivitamin
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