Zettner A, Boss G R, Seegmiller J E
Ann Clin Lab Sci. 1981 Nov-Dec;11(6):516-24.
Large daily doses of oral folic acid ranging from 25 to 1,000 mg and totalling between 1,875 and 16,000 mg per course of treatment were well tolerated without any evidence of toxic effects by four hyperuricemic men of the ages of 26, 38, 46 and 50 years. The minimum folate absorption in the gut as measured by urinary excretion ranged from 10.1 to 45.7 percent. The percentage of absorption within a give patient remained similar in successive courses and there was no evidence of saturation of the absorption process related to dose or time. The pattern of urinary excretion of folates did not indicate that appreciable fractions relative to the large folate doses were retained by the patients. Serum, erythrocyte, and urine folates returned to pretreatment levels within 120 days after treatment. These findings suggest that the folate stores of the body do not expand by orders of magnitude even when megadoses of folates are absorbed in the gut. The rise of the folate levels in erythrocytes was gradual and continuous during treatment and is best explained by postulating that incorporation of folate into red cell takes place mostly at the precursor and reticulocyte stages. The decrease of erythrocyte folate values seen 40 to 66 days after folate treatment indicates that the folate content of erythrocytes diminishes during their life span.
年龄在26、38、46和50岁的4名高尿酸血症男性，每日口服大剂量叶酸，剂量范围为25至1000毫克，每个疗程总量在1875至16000毫克之间，耐受性良好，未出现任何中毒效应迹象。通过尿排泄量测定，肠道内叶酸的最低吸收率在10.1%至45.7%之间。同一患者在连续疗程中的吸收百分比保持相似，没有证据表明吸收过程与剂量或时间相关的饱和现象。叶酸的尿排泄模式并未表明患者相对于大剂量叶酸保留了可观的部分。治疗后120天内，血清、红细胞和尿液中的叶酸水平恢复到治疗前水平。这些发现表明，即使肠道吸收了大剂量叶酸，人体的叶酸储备也不会成数量级地增加。治疗期间红细胞中叶酸水平的升高是逐渐且持续的，最好的解释是假设叶酸主要在红细胞前体和网织红细胞阶段掺入红细胞。叶酸治疗后40至66天红细胞叶酸值的下降表明，红细胞中的叶酸含量在其生命周期内会减少。
