EFFECT OF METHOTREXATE ON VITAMIN B6 DEFICIENCY IN RHEUMATOID ARTHRITIS

本研究的目的是通过蛋氨酸和色氨酸负荷试验以及测量血液中维生素B水平来确定类风湿关节炎（RA）患者接受或不接受甲氨蝶呤（MTX）治疗时B族维生素的状况。最近，我们发现RA和血浆PLP水平低的患者也有高同型半胱氨酸水平，无论是空腹还是口服蛋氨酸挑战，都比健康受试者高。高同型半胱氨酸血症是中风和冠心病的一个新认识的危险因素，可能是解释RA患者死亡率增加的重要原因。我们假设RA中PLP缺乏导致PLP依赖性代谢途径紊乱。我们假设MTX阻断了对蛋氨酸激射试验的反应，但在MTX治疗的患者中仍然存在PLP缺乏，并且这种缺乏可以通过色氨酸激射试验来确定。本研究将：a.确定20例服用MTX的RA患者、20例未服用MTX的患者和20例年龄匹配的健康对照者对蛋氨酸和色氨酸挑战的反应；B.通过对健康对照者服用萘普生两周后重新检测非甾体类抗炎药物对色氨酸激发试验的影响；c.确定血浆PLP水平是否可以可靠地预测RA患者维生素B6缺乏症；d.测试1个月口服维生素B6治疗使检测结果异常的患者蛋氨酸和色氨酸挑战结果正常化的能力。

The purpose of this study is to determie the status of B vitamins in rheumatoid arthritis (RA) patients with or without methotrexate (MTX) treatment by methionine and tryptophan load tests, and by measuring vitamin B levels in the blood. Recently, we have found that patients with RA and low plasma PLP levels also have elevated homocysteine levels, both fasting and in response to an oral methionine challange, than do healthy subjects. Hyper-homocysteinemia is a newly recognized risk factor for stroke and coronary heart disease, and may be important in explaining the increased mortality rate of patients with RA. We hypothesize that PLP deficiency in RA causes disorders of PLP-dependent metabolic pathways. We hypothesize that MTX blocks the response to the methionine challenge test, but that PLP deficiency nonetheless exists in patients treated with MTX, and that this deficiency can be identified using a tryptophan challenge test. This study will: a. determine the response to methionine and tryptophan challenge in 20 patients with RA taking MTX, 20 patients not taking MTX, and 20 age-matched healthy controls; b. determine the effect of nonsteroidal anti-inflammatory medication on the tryptophan challenge test by re-testing the healthy control subjects after two weeks of treatment with naproxen; c. determine whether there is a level of plasma PLP which can reliably predict vitamin B6 deficiency in patients with RA; d. test the ability of 1 month of oral vitamin B6 therapy to normalize methionine and tryptophan challenge results in those patients with abnormal tests.