Til H P, Kuper C F, Falke H E, Bär A
TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S221-31. doi: 10.1006/rtph.1996.0102.
Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10 male and 10 female Swiss CD-1 mice and four groups of 15 male Wistar Crl:(WI) WU BR rats at dietary levels of 0, 5, 10, or 20% for 90 days. A fifth group of rats received a diet containing 20% erythritol on a time-restricted basis (6 hr/day), and a sixth group received a diet containing 20% mannitol for comparison. There were no treatment-related mortalities in either mice or rats. Soft stools and occasional diarrhea were observed in rats fed diets with 20% erythritol or mannitol but not in mice. Body weights were slightly yet significantly reduced in rats fed 20% erythritol or mannitol and in male mice of the 20% dose group. Erythritol intake in the high-dose group was approximately 12 g/kg body wt in rats and 44 and 45 g/kg body wt in male and female mice, respectively. Hematological and clinicochemical examinations of blood and plasma did not reveal any treatment-related effects. Urine output increased with increasing erythritol dose. In male and female mice of the 20% erythritol group, the creatinine-normalized urinary excretion of protein, K-glutamyltransferase (GGT), and electrolytes (Na+, K+, Ca2+, Pi, citrate) was significantly increased while urinary N-acetylglucosaminidase (NAG) remained unchanged. At the 10% level, significantly increased urinary protein (both sexes) and GGT (males only) excretion were seen. In rats, the creatinine-normalized urinary excretion of GGT, NAG, and some electrolytes (Na+, K+, and Ca2+) was increased in some erythritol groups but a clear dose-response relationship was evident only for calcium. On termination of the study, cecal enlargement was seen in rats of the 10 and 20% dose groups and in mice of the 20% dose group. Increased relative and absolute kidney weights were observed in both sexes of mice in the 20% erythritol group, in male mice of the 5 and 10% groups, and in rats of the 10 and 20% erythritol groups. Histopathological examination did not reveal any treatment-related abnormalities in either mice or rats. In conclusion, the ingestion of erythritol for 90 days at dietary levels of up to 20% did not produce signs of toxicity in mice or rats. In particular, the morphological integrity of the kidneys was not adversely affected by the treatment in either species. The increases in urinary excretion of protein, GGT, NAG, and electrolytes were considered to result from extensive osmotic diuresis and a potential overload of the renal excretory system at the high dose levels employed.
赤藓糖醇是一种糖醇（多元醇），有作为低热量填充甜味剂的潜在应用价值。摄入的赤藓糖醇能被有效吸收，并以未改变的形式通过尿液排出，因为它不会被动物或人体进行全身代谢。将赤藓糖醇以0%、5%、10%或20%的膳食水平给予四组每组10只雄性和10只雌性瑞士CD - 1小鼠，以及四组每组15只雄性Wistar Crl:(WI) WU BR大鼠，持续90天。第五组大鼠在限时（每天6小时）的基础上接受含20%赤藓糖醇的饮食，第六组接受含20%甘露醇的饮食作为对照。小鼠和大鼠中均未出现与处理相关的死亡情况。在喂食含20%赤藓糖醇或甘露醇饮食的大鼠中观察到软便和偶尔的腹泻，但在小鼠中未观察到。喂食20%赤藓糖醇或甘露醇的大鼠以及20%剂量组的雄性小鼠体重略有但显著降低。高剂量组大鼠的赤藓糖醇摄入量约为12 g/kg体重，雄性和雌性小鼠分别为44和45 g/kg体重。血液和血浆的血液学及临床化学检查未发现任何与处理相关的影响。尿量随赤藓糖醇剂量增加而增加。在20%赤藓糖醇组的雄性和雌性小鼠中，经肌酐标准化后的尿蛋白、γ-谷氨酰转移酶（GGT）和电解质（Na +、K +、Ca2 +、Pi、柠檬酸盐）排泄显著增加，而尿N - 乙酰葡糖胺酶（NAG）保持不变。在10%水平时，观察到尿蛋白（两性）和GGT（仅雄性）排泄显著增加。在大鼠中，一些赤藓糖醇组经肌酐标准化后的尿GGT、NAG和一些电解质（Na +、K +和Ca2 +）排泄增加，但仅钙呈现明显的剂量反应关系。在研究结束时，在10%和20%剂量组的大鼠以及20%剂量组的小鼠中观察到盲肠肿大。在20%赤藓糖醇组的两性小鼠、5%和10%组的雄性小鼠以及10%和20%赤藓糖醇组的大鼠中观察到肾脏相对和绝对重量增加。组织病理学检查未发现小鼠或大鼠中有任何与处理相关的异常。总之，在膳食水平高达20%的情况下摄入赤藓糖醇90天，未在小鼠或大鼠中产生毒性迹象。特别是，两种动物的肾脏形态完整性均未受到处理的不利影响。蛋白质、GGT、NAG和电解质尿排泄增加被认为是由于大量渗透性利尿以及在所采用的高剂量水平下肾排泄系统的潜在过载所致。
